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Shortening the duration of the viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is critical to controlling viral transmission, alleviating the burden on the healthcare system, and ultimately mitigating the impact of the pandemic. This randomized, single‐blind, placebo‐controlled clinical trial aimed to investigate the safety and efficacy of gargling with plasma‐activated water (PAW) on prolonged viral shedding in patients infected with SARS‐CoV‐2 Delta and Omicron variants. Sixty‐two subjects, aged 18–80 years and infected with SARS‐CoV‐2, were recruited at two coronavirus disease 2019 (COVID‐19)‐designated hospitals in Shaanxi from January to March 2022. Primary outcomes included cumulative conversion rates, incidence of adverse reactions, and biosafety parameters. Results suggested that PAW gargling treatment might contribute to reducing the duration of SARS‐CoV‐2 Delta and Omicron variant infections and alleviating symptoms. [ABSTRACT FROM AUTHOR]

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. • circRara was upregulated after LPS or poly (I: C) treatment in miiuy croaker. • circRara promote NF-κB and IRF3 signaling pathways. • circRara enhances the expression of inflammatory cytokines and antiviral genes. [ABSTRACT FROM AUTHOR]

Fiber quality is a major breeding goal in cotton, but phenotypically direct selection is often hindered. In this study, we identified fiber quality and yield related loci using GWAS based on 2.97 million SNPs obtained from 10.65× resequencing data of 1081 accessions. The results showed that 585 novel fiber loci, including two novel stable SNP peaks associated with fiber length on chromosomes At12 and Dt05 and one novel genome regions linked with fiber strength on chromosome Dt12 were identified. Furthermore, by means of gene expression analysis, GhM_A12G0090 , GhM_D05G1692 , GhM_D12G3135 were identified and GhM_D11G2208 function was identified in Arabidopsis. Additionally, 14 consistent and stable superior haplotypes were identified, and 25 accessions were detected as possessing these 14 superior haplotype in breeding. This study providing fundamental insight relevant to identification of genes associated with fiber quality and yield will enhance future efforts toward improvement of upland cotton. • A total of 909 novel fiber and yield loci were detected via WGRS with 10.65× coverage depth in 1,081 cotton accessions. • Three novel stable SNP peaks associated with FL and FS were found. • GhM_D11G2208 can promote cell elongation based up leaf trichome and dark-grown hypocotyls in Arabidopsis. • 14 consistent and stable superior haplotypes were detected based on 915 SNPs in Dt11 region. [ABSTRACT FROM AUTHOR]

GO membranes cross-linked by copper ion and intercalated with tannic acid exhibit superior ionic sieving performance and aqueous stability. The fabrication strategy is novel and simple. [Display omitted] • GO membranes cross-linked by copper ion and tannic acid are successfully prepared. • The aqueous stability and permeance of membranes are improved simultaneously. • Outstanding membrane performance for K+/Mg2+ and K+/Cr3+ separation. • GO-Cu-TA 20 membrane exhibits a high K+ ion penetration rate of 0.75 mol m-2 h-1. • The membranes have great potentials in lithium extraction from salt lakes etc. Graphene oxide (GO) membranes have exhibited excellent molecular sieving properties in several areas, such as water treatment and gas separation, but unsatisfactory permeability and/or selectivity for ionic separation. Meanwhile, the instability of pure GO membranes in acidic solution has significantly impeded the ionic sieving applications. In this study, a kind of GO composite membranes (GO-Cu-TA a) with exceptional aqueous stability and superior ionic sieving properties are successfully prepared by employing a unique natural deposition strategy to introduce copper ions and tannic acid (TA). Based on the synergistic effect of the two cross-linking agents of copper ion and TA, the structural stability and ionic sieving performance of GO-Cu-TA a membranes are obviously enhanced. The resultant membrane with 20% TA loading displays excellent ionic sieving performance in a mixed solution containing K+, Mg2+ and Cr3+ three metal cations, and the selectivities of K+/Mg2+ and K+/Cr3+ are 46.43 and 185.32, respectively. Especially, the permeation rate of K+ ion reaches up to 0.75 mol m-2 h-1. Meanwhile, the ionic sieving property of such GO membranes possesses outstanding reusability and long-term stability. Such a membrane can also effectively separate mono-/multivalent metal cations from the mixed solution contained of the nine metal cations. The selectivities of monovalent/divalent metal cations (such as K+/Pb2+, K+/Ca2+, K+/Mg2+) are as high as 7.69–51.49, and those of monovalent/trivalent metal cations (such as K+/Fe3+, K+/Cr3+, K+/Al3+) are as high as 247.62–346.67. These results indicate that the GO-Cu-TA a membranes fabricated by the method of natural deposition strategy are expected to be used in the practical applications of lithium extraction from Salt Lake and wastewater purification, etc. [ABSTRACT FROM AUTHOR]

Anatomical sectionectomy based on Takasaki's segmentation has shown advantages in hepatocellular carcinoma. However, whether this approach improves the survival of intrahepatic cholangiocarcinoma (ICC) remains unknown. A series of 248 consecutive patients with solitary ICCs who underwent hepatectomy were studied retrospectively. The patients were classified into the groups of anatomical sectionectomy based on Takasaki's segmentation (TS group) and non-Takasaki's hepatectomy (NTH group). The bias between the two groups was minimized using propensity score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan–Meier analysis. The Cox proportional hazards model was performed to determine the adverse risk factors associated with survival. After PSM, 67 pairs of patients were compared. Both the RFS and OS rates in the TS group were significantly better than those in the NTH group (23.2 % vs. 16.5 %, and 40.4 % vs. 27.3 %, P = 0.035 and 0.032, respectively). Multivariate analysis showed that NTH was independently associated with worse RFS and OS than TS. The stratified analysis demonstrated that the RFS and OS rates in the TS group with tumor stage I and tumor size ≥3 cm were significantly better than those in the NTH group, while the survival rates for ICC with stage I and tumor size <3 cm or stage II-III showed no significant difference. TS was associated with improved RFS and OS in patients with solitary ICC even after PSM. TS may be preferred particularly in patients with tumor stage I and tumor size ≥3 cm. [ABSTRACT FROM AUTHOR]

Background: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma.Methods: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed.Findings: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported.Interpretation: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma.Funding: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University.Translation: For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Gigantol, a naturally occurring dibenzyl compound derived from various orchid species within the Dendrobium genus, exhibits notable pharmacological activity. We found that gigantol has significant anti-lung cancer properties, both in vitro and in vivo, which it exerts through the induction of ferroptosis. Furthermore, we found gigantol's specific interaction with the subunit solute carrier family 7 member 11 (SLC7A11) within the cystine/glutamate antiporter system (system Xc−), leading to the inhibition of glutathione (GSH) synthesis. This, in turn, disrupts redox homeostasis. Additionally, gigantol hinders the uptake of extracellular cystine via lung cancer cells, resulting in reduced cellular levels of cysteine, a vital precursor in GSH synthesis. This reduction, in turn, leads to an increase in the levels of glutamate. Simultaneously, our study reveals that the decrease in GSH significantly inhibits the activity of glutathione peroxidase 4 (GPX4), a key enzyme within the antioxidant system. Remarkably, N-acetylcysteine, a cystine precursor, effectively reverses gigantol-induced ferroptosis in lung cancer cells. This provides further confirmation that the anti-lung cancer mechanism of gigantol is to induce ferroptosis of lung cancer cells by targeting the SLC7A11-GPX4 signaling axis. In conclusion, our study underscores gigantol's potential as a promising candidate drug for the treatment of patients with lung cancer in clinical practice. • Gigantol exerts anti-lung cancer effect in vitro and in vivo. • Gigantol induces ferroptosis in lung cancer cells. • Gigantol via targeting SLC7A11-GPX4 axis induces ferroptosis in lung cancer cells. • NAC via activate SLC7A11 alleviates the inhibitory effect of Gigantol on lung cancer cells. [ABSTRACT FROM AUTHOR]

This article, published in the British Journal of Surgery, examines the importance of nodular number in predicting the prognosis of patients with intermediate-stage hepatocellular carcinoma (HCC) who undergo hepatectomy. The study, conducted at multiple hepatobiliary centers in China, Italy, and the USA, analyzed data from HCC patients who had undergone curative-intent hepatic resection between 2008 and 2018. The findings indicate that patients with three or more tumor nodules had lower overall survival and recurrence-free survival rates compared to those with two nodules. The study suggests that nodular number should be considered when predicting long-term prognosis after hepatic resection for intermediate-stage HCC. However, further research is needed to validate these findings. The study was supported by various funding sources and the authors have no conflicts of interest. [Extracted from the article]

X-linked Alport syndrome (XLAS) is a common hereditary nephropathy caused by COL4A5 gene mutations. To date, many splice site mutations have been described but few have been functionally analyzed to verify the exact splicing effects that contribute to disease pathogenesis. Here, we accidentally discovered 2 COL4A5 gene splicing mutations affecting the same residue (c.2917+1G>A and c.2917+1G>C) in 2 unrelated Chinese families. In vitro minigene assays showed that the 2 mutations produced 3 transcripts in H293T cells: one with a 96-bp deletion in exon 33, one with exon 33 skipping, and one with exon 33-34 skipping. However, fragment analysis results showed that the main splicing effects of the 2 mutations were different, the c.2917+1G>A mutation mainly activated a cryptic donor splice site in exon 33 and resulted in the deletion of 96 bp in exon 33, while the c.2917+1G>C mutation mainly caused exon 33 skipping. Our findings indicate that different nucleotide substitutions at the same residue can cause different splicing effects, which may contribute to the variable phenotype of Alport syndrome. [ABSTRACT FROM AUTHOR]

The synthesis and crystal structures of 3,5‐dinitro‐1H‐pyrazolyl‐4‐carboxylic acid (H2dnpzc) and its four complexes with Ca2+, Ba2+, Na+ and K+ are reported in this paper. Ca(dnpzc)·5H2O exhibits a 1D polymeric structure, whereas Ba(dnpzc)·4H2O possesses a 2D structure. The structure of Na2(dnpzc)·4H2O consists of 2D layers of [Na(dnpzc)]–n and 1D chains of [Na(H2O)3]+n. K2(dnpzc)·H2O has a true 3D structure. It was observed that the doubly deprotonated ligand (dnpzc2–) can act as a versatile bridge to form polymeric structures by varying combinations of its 8 potential donor atoms (two carboxy O atoms, two pyrazolyl N atoms and four nitro O atoms). Particularly in the structure of K2(dnpzc)·H2O, all the 8 donor atoms of dnpzc2– take part in the coordination and as many as 10 potassium atoms are connected by one ligand. [ABSTRACT FROM AUTHOR]

Pure lead powder can be electrodeposited by reduction of lead ions (Pb2+) in aqueous electrolyte. In this investigation, ultra-fine lead powders with a minimum median diameter of 4.5 μm were electrodeposited in acetate solution. The formation mechanism of lead oxide (PbO) during electrodeposition was proposed. Operation parameters such as pH value, current density, and gelatin had remarkable influence on oxidation degree, median diameter, and current efficiency, which were detailed for the first time. Metallic Pb was formed with strong (111) preferred orientation, and micrography, composition, and structure were characterized. Amorphous PbO was found in as-deposited lead powder, and a gel-layer process was proposed to elucidate the formation of PbO. It was suggested the Pb···OH was the most important intermediate state to form PbO and the gel-layer played the key role in generation of pure lead powder. [ABSTRACT FROM AUTHOR]

The main purpose of this paper is using the analytic method and the properties of the character sums to study the computational problem of one kind hybrid power mean involving the character sums of polynomials and the two-term exponential sums, and give several interesting identities and asymptotic formulae for them. [ABSTRACT FROM AUTHOR]

Yixin Ningshen tablet is a CFDA-approved TCM formula for treating coronary heart disease (CHD) clinically. However, its active compounds and mechanism of action in treating CHD are unknown. In this study, a novel strategy with the combination of network pharmacology and proteomics was proposed to identify the active components of Yixin Ningshen tablet and the mechanism by which they treat CHD. With the application of network pharmacology, 62 active compounds in Yixin Ningshen tablet were screened out by text mining, and their 313 potential target proteins were identified by a tool in SwissTargetPrediction. These data were integrated with known CHD-related proteomics results to predict the most possible targets, which reduced the 313 potential target proteins to 218. The STRING database was retrieved to find the enriched pathways and related diseases of these target proteins, which indicated that the Calcium, MAPK, PI3K-Akt, cAMP, Rap1, AGE-RAGE, Relaxin, HIF-1, Prolactin, Sphingolipid, Estrogen, IL-17, Jak-STAT signaling pathway, necroptosis, arachidonic acid metabolism, insulin resistance, endocrine resistance, and steroid hormone biosynthesis might be the main pathways regulated by Yixin Ningshen tablet for the treatment of CHD. Through further enrichment analysis and literature study, EGFR, ERBB2, VGFR2, FGF1, ESR1, LOX15, PGH2, HMDH, ADRB1, and ADRB2 were selected and then validated to be the target proteins of Yixin Ningshen tablet by molecular docking, which indicated that Yixin Ningshen tablet might treat CHD mainly through promoting heart regeneration, new vessels' formation, and the blood supply of the myocardial region and reducing cardiac output, oxygen demand, and inflammation as well as arteriosclerosis (promoting vasodilation and intraplaque neoangiogenesis, lowering blood lipid). This study is expected to benefit the clinical application of Yixin Ningshen tablet for the treatment of CHD. [ABSTRACT FROM AUTHOR]

IMB5036 is a pyridazinone compound with antiproliferative and antitumour activity against hepatoma and pancreatic cancer. In this study, we attempted to identify the target protein of IMB5036 and test its potential for overcoming multidrug resistance and inducing pyroptosis. We examined the effects of IMB5036 on cancer cells by in vitro assays, a molecular docking model and in vivo tumour models. We performed pull-down experiments using biotinylated IMB5036 and identified the binding proteins. Gene knockdown were used to investigate the oncogenic role of KH-type splicing regulatory protein (KSRP). Western blot was used to detect for mechanism-associated molecules. IMB5036 could overcome resistance to multiple chemotherapeutic drugs at the cellular level and in vivo. Furthermore, IMB5036 was not a P-glycoprotein (P-gp) substrate and downregulated the expression of P-gp. We identified KSRP as a binding protein of IMB5036. The knockdown of KSRP inhibited the proliferation of MCF7 and MCF7/adriamycin (MCF7/ADR) cells. In addition, IMB5036 induced pyroptosis in both MCF7 and MCF7/ADR cells via KSRP. We found IMB5036 binds to KSRP and overcomes multidrug resistance via gasdermin E (GSDME)-dependent pyroptosis. [Display omitted] [ABSTRACT FROM AUTHOR]

The main purpose of this paper is using the analytic methods, the solutions of the congruence equation mod p and the properties of Gauss sums to study the computational problem of one kind fourth power mean of the general 3-dimensional Kloostermann sums mod p, and give a sharp asymptotic formula for it. [ABSTRACT FROM AUTHOR]

A neutral polysaccharide coded as CERP1 was extracted and purified from the residue of Codonopsis pilosula by ethanol precipitation and column chromatography. The structure of CERP1 was determined by HPAEC-PAD, HPLC, HPSEC-MALLS, FT-IR, NMR, and TEM. The results showed that CERP1 was a heteropolysaccharide composed of Arabinose, Glucose, and Galactose in the ratio of 1.00:19.83:6.94. HPSEC-MALLS showed that CERP1 was homogeneous with an absolute molecular weight of 4.840 × 10 3  Da. The NMR results and the GC–MS result of methylation indicated that 1-linked β- d -glucose, 1,3-linked β- d -glucose, 1,6-linked β- d -glucose and 1,3,6-linked β- d -galactose were the main linkages in CERP1. TEM results indicated that CERP1 had a homogeneous particle size and good dispersibility both in purified water and 0.05 M sodium sulfate. Pre-treatment with CERP1 could result in a significant improvement of the insulin secretion of the INS-1 cells. While in vivo assays, CERP1 exhibited a potent hypoglycemic effect on T2DM mice for its ability to relieve oxidative stress, ameliorate lipid metabolism, increase glycolytic enzyme activity as well as decrease liver transaminase activity. This study gives a chance for exploring the residue of Codonopsis pilosula. [ABSTRACT FROM AUTHOR]

Inhibitor of DNA-binding 3 (ID3) is a helixloop-helix transcription factor that is associated with cell proliferation, differentiation and drug resistance in human cancer, and with anticancer effects in certain types of cancer cells. The present study investigated whether and how ID3 was involved in multidrug resistance (MDR) in human cisplatin (DDP)-resistant A549/DDP lung adenocarcinoma cells. The underlying mechanism of action was investigated in vitro. Cell Counting Kit-8 (CCK-8) and flow cytometry assays demonstrated that overexpression of ID3 enhanced chemosensitivity and decreased drug efflux in A549/DDP cells. Reverse transcription-quantitative polymerase chain reaction revealed that the expression of anti-apoptotic gene B-cell lymphoma-2 was significantly downregulated in cells expressing exogenous ID3 (P<0.05). These results indicated that ID3 may synergize with DDP to increase apoptosis in A549/DDP cells. ID3 overexpression modulated the activity of phosphoinositide 3-kinase/RAC serine/threonine-protein kinase signaling and downregulated the expression of multi-drug resistance protein-1, indicating that ID3 expression can reverse multi-drug resistance in A549/DDP cells. Collectively, these results indicate that ID3 is a potential effective chemotherapeutic target for the treatment of human DDP-resistant A549 lung adenocarcinoma therapy. [ABSTRACT FROM AUTHOR]

In recent years, many studies have shown that long non-coding RNAs (lncRNAs) can regulate many biochemical processes, such as cell growth, proliferation, and immune response, which have attracted great attention. There are relatively many studies on lncRNA in mammals, while the research on lncRNA in lower vertebrates has just begun. In this study, we found a lncRNA, lncRNA LTCONS8875, related to innate immune response in Miichthys miiuy (miiuy croaker). Our results showed that lncRNA LTCONS8875 can up-regulate the expression of IRAK4 at the mRNA and protein levels, and significantly increase the production of inflammatory factors under LPS stimulation. Our research also confirmed that lncRNA LTCONS8875 plays an active role in regulating inflammation, cell proliferation, and cell viability. In summary, this research results showed that lncRNA LTCONS8875 can as an active regulatory role of innate immunity in miiuy croaker by up-regulating the expression of IRAK4, providing some insights for understanding the network mechanism of non-coding regulation of fish immunity. • lncRNA LTCONS8875 can up-regulate the mRNA and protein levels of IRAK4. • lncRNA LTCONS8875 can promote the production of inflammatory factors. • lncRNA LTCONS8875 is a key positive regulator of innate immune response. [ABSTRACT FROM AUTHOR]

The protein-coding ability of circRNAs has recently been a hot topic, but the role of protein-coding circRNAs in antiviral innate immunity of teleost fish has rarely been reported. Here, we identified a novel circRNA, termed circMORC3, derived from Microrchidia 3 (MORC3) gene in Miichthys miiuy. circMORC3 can inhibit the expression of antiviral cytokines. In addition, circMORC3 encodes a novel peptide with a length of 84 amino acids termed MORC3-84aa. MORC3-84aa not only significantly inhibited TRIF-mediated activation of IRF3 and NF-κB signaling pathways, but also effectively suppressed the expression of antiviral cytokines triggered by RNA virus Siniperca chuatsi rhabdovirus (SCRV). We found that MORC3-84aa directly interacted with TRIF and negatively regulated TRIF protein expression. In addition, host gene MORC3 attenuates SCRV-induced IFN and ISG expression. Mechanistically, MORC3-84aa promotes autophagic degradation of TRIF by enhancing K6-linked ubiquitination and inhibits TRIF-mediated activation of the type I interferon signaling pathway. And the host gene MORC3 not only repressed IRF3 protein expression but also inhibited IRF3 phosphorylation levels. Our study shows that circMORC3 and host gene MORC3 played a synergistic role in viral immune escape. Author summary: Increasing evidence indicates that circRNAs have important functions, but the relationship between circRNAs encoded protein and TLR signaling pathway remains unknown, particularly in lower vertebrates. Here, we identified a circRNA-encoded protein that synergistically regulates the TLR signaling pathway with the host gene. Our results provided direct evidence that circMORC3 could negatively regulate TRIF by autophagic degradation through its encoded protein MORC3-84aa. In addition, we found that the host gene MORC3 can inhibit IRF3 protein expression and its phosphorylation level. Collectively, these findings provide important insights regarding the functional importance of circMORC3 and the host gene in viral immune escape. [ABSTRACT FROM AUTHOR]

5-butyl-3,9-difluoro-5 H -benzimidazo[1,2- a ]benzimidazole was designed and synthesized, its structure was characterized by infrared spectroscopy (IR) and nuclear magnetic resonance ( 1 H NMR, 13 C NMR) spectroscopy. Optical properties including UV–vis absorption and fluorescence emission spectra of the title compound were investigated experimentally. The results showed the title compound can absorb UV light at 314 nm and exhibit UV fluorescence emission at 341 nm. Theoretical studies on molecular structure, IR, 1 H NMR, 13 C NMR, frontier molecular orbitals, UV–vis absorption and fluorescence emission of the synthesized compound had been carried out by using Gaussian 09 program with DFT method. Calculations on molecular structure and vibrational frequency were carried out at B3LYP/6-311G(d,p) level. Nuclear magnetic resonance chemical shifts were performed by DFT MPW1PW91/6-311 + G(2d,p) method. UV–vis absorption and fluorescence emission were simulated with TD-DFT method at PBEPBE/6-311 + G(d,p) level. The comparison between experimental and theoretical results indicates good coincidences between them, which prove that the chosen theoretical methods are reliable for the properties prediction of other structurally similar compounds, especially for those whose properties are difficult to be measured experimentally. The results also clue the title compound a candidate dye with high fluorescence quantum yield for its small Stokes' shift and structural stacking protection. [ABSTRACT FROM AUTHOR]

In recent years, more and more researchers have devoted to the study of circular RNAs (circRNAs) in noncoding RNAs. As an important regulator in a variety of biological processes, circRNAs are relatively abundant in the study of mammals, while research in lower vertebrates is still lacking. In this study, we found a circRNA, circPlce1, related to innate immune response in Miichthys miiuy (miiuy croaker). The experimental results confirmed that circPlce1 could promote the production of antiviral genes and inflammatory response under the stimulation of poly (I: C) and LPS. We also confirmed that circPlce1 can promote NF-κB and IRF3 pathways through luciferase reporter assay experiment. In addition, we also found that circPlce1 can promote cell proliferation and improve cell viability. In conclusion, our results showed that circPlce1 plays an active role in regulating inflammatory response, cell proliferation and cell viability, providing a foundation for the study of the biological function of circRNAs in the innate immune response in teleost fish. • circPlce1 was up-regulated in M. miiuy spleen after stimulation with poly (I: C) and LPS. • circPlce1 plays an active role in regulating antiviral and inflammatory response. • circPlce1 regulates NF-κB and IRF3 signaling pathway. [ABSTRACT FROM AUTHOR]

As a non-coding RNA with regulatory functions, microRNAs(miRNAs) can regulate gene expression and participate in a variety of physiological and pathological processes. In recent years, although there have been many studies on miRNA, the regulation mechanisms of miRNA in teleost fish have not been fully elucidated. In this study, it was first predicted that MITA is the target of miR-27c through bioinformatics, and it was confirmed by dual fluorescence experiments. Then we found that miR-27c can inhibit the expression of MITA at the mRNA and protein levels, thereby promoting the NF-κB or IRF3 pathway. It is speculated that miR-27c plays an important role in the innate immunity of teleost fish. This study will help to further understand miRNAs regulatory mechanism in teleost fish. • miR-27c targeted regulation of important mediators MITA in miiuy croaker. • miR-27c inhibits NF-κB and IRF3 signal pathways. • miR-27c suppresses innate immune response by inhibiting MITA. [ABSTRACT FROM AUTHOR]

The inherent safety functions will mitigate the consequences of the accidents, and it can be accomplished through the passive safety systems which employed in the typical pressurized water reactor (PWR). In this paper, a new passive residual heat removal system (PRHRS) is designed for a typical nuclear power plant. PRHRS consists of a steam generator (SG), a cooling tank with two groups of cooling pipes, an air-cooling heat exchanger (AHX), an air-cooling tower, corresponding pipes and valves. The cooling tank which works as an intermediate buffer device is used to transfer the core decay heat to the AHX, and then the core decay heat will be removed to the atmosphere finally. The RELAP5/MOD3.4 code is used to analyze the operation characteristics of PRHRS and the primary loop system. It shows PRHRS could remove the decay heat from the primary loop effectively, and the natural circulations can be established in the primary circuit and the PRHRS circuit respectively. Furthermore, the sensitivity study has also been done to research the effect of various factors on the heat removal capacity. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Rehmanniae Radix (RR) and Cornus officinalis (CO) are two traditional Chinese medicines widely used in China for treating diabetes mellitus and its complications, such as diabetic nephropathy. Iridoid glycoside of Cornus officinalis (IGCO), triterpenoid acid of Cornus officinalis (TACO) and iridoid glycoside of Rehmanniae Radix (IGRR) formed an innovative formula named combinatorial bioactive parts (CBP). The aims of the present study were to investigate the renoprotective effects of CBP on DN through the inhibition of AGEs/RAGE/SphK1 signaling pathway activation, and identify the advantage of CBP compared with IGCO, TACO, IGRR. Materials and methods The db/db diabetic renal injury model was used to examine the renoprotective effects of CBP, IGCO, TACO and IGRR. For mechanistic studies, diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGEs/RAGE/SphK1 pathway were determined. Results CBP, IGCO, TACO and IGRR inhibited the decrease in serum insulin levels and the increases in urine volume, food consumption, water intake, TC, TG, glycated serum protein, fasting blood glucose levels, 24 h urine protein levels, and serum levels of urea nitrogen and creatinine. It also prevented ECM accumulation and improved the histology of pancreas and kidney, and alleviated the structural alterations in mesangial cells and podocytes in renal cortex. Moreover, CBP, IGCO, TACO and IGRR down-regulated the elevated staining, protein levels of RAGE, SphK1, TGF-β and NF-κB. Among the treatment groups, CBP produced the strongest effects. Conclusions These findings suggest that the inhibitory effect of CBP, IGCO, TACO and IGRR on the activation of AGEs/RAGE/SphK1 signaling pathway in db/db diabetic mice kidney is a novel mechanism by which CBP, IGCO, TACO and IGRR exerts renoprotective effects on DN. Among all the groups, CBP produced the strongest effect while IGCO, TACO and IGRR produced weaker effects. [ABSTRACT FROM AUTHOR]

Silver (Ag)-containing agents or materials are widely used today in plant protection for their antimicrobial activity. In view of the superior inhibitory ability of biosynthesized (aldehyde-modified sodium alginate based) silver nanoparticles (AgNPs) against plant pathogenic fungi in our previous research, here we explored the antagonistic effect of biosynthesized AgNPs on plant pathogenic bacteria and the underlying mechanism. We selected Pseudomonas syringae pv. tabaci, the causal agent of tobacco wildfire disease, as the target and found that 1.2 μg/mL biosynthesized AgNPs completely inhibited the growth of P. syringae pv. tabaci in vitro and in vivo by partly destroying the cell membrane structure of the pathogen, resulting in cytoplasmic leakage. Moreover, Nicotiana benthamiana treated with 1.2 μg/mL biosynthesized AgNPs exhibited a significant upregulation of nonexpressor of pathogenesis-related genes 1 (NPR1) and pathogenesis-related gene 2 (PR2), the typical markers of the salicylic acid (SA)-mediated defense system, and an increase in peroxidase (POD) and polyphenol oxidase (PPO) activities as well as the production of reactive oxygen species (ROS). Furthermore, biosynthesized AgNPs treatment increased the chlorophyll content and dry weight of N. benthamiana. Overall, we demonstrated that biosynthesized AgNPs at a low concentration have high inhibitory effect on the pathogen causing tobacco wildfire disease by destroying bacterial cell membrane and inducing defense resistance in host plant. These results lay a theoretical foundation for further application of biosynthesized AgNPs in the control of plant bacterial diseases. [ABSTRACT FROM AUTHOR]

Avilamycin is one of EU-approved antimicrobial agents in feed industry to inhibit the growth of multidrug-resistant Gram-positive bacteria. Here, we applied a process of combining ribosome engineering and genome shuffling to achieve rapid improvement of avilamycin production in Streptomyces viridochromogenes AS 4.126. The starting mutant population was generated by Co γ-irradiation treatments of the spores. After five rounds of protoplast fusion with streptomycin-resistance screening, an improved recombinant E-219 was obtained and its yield of avilamycin reached 1.4 g/L, which was increased by 4.85-fold and 36.8-fold in comparison with that of the shuffling starter Co γ-316 and the ancestor AS 4.126. Furthermore, the mechanism for the improvement of shuffled strains was investigated. Recombinants with enhanced streptomycin resistance exhibited significantly higher avilamycin production and product resistance, probably due to the mutations in the ribosome protein S12. The morphological difference between the parent mutant and shuffled recombinant was observed in conidiospore, and hyphae pellets. The presence of genetic diversity among shuffled populations with varied avilamycin productivity was confirmed by randomly amplified polymorphic DNA analysis. In summary, our results demonstrated that genome shuffling combined with ribosome engineering was a powerful approach for molecular breeding of high-yield industrial strains. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to develop a novel intravascular loopless monopole antenna (ILMA) design specifically for imaging of small vessel walls. The ILMA consisted of an unshielded, low-friction guide wire and a tuning/matching box. The material of the guide wire was nitinol and it was coated with polyurethane. Because the guide wire was unshielded, it could be made thinner than the coaxial cable-based loopless intravascular antenna design. The material of the box was aluminum. In this study, the diameter of the guide wire was 0.5 mm and the length was 58.7 mm. The ILMA was used as a receiving antenna and body coil for transmission. To verify the feasibility of the ILMA, in vitro and in vivo experiments were performed on a 3.0-T magnetic resonance (MR) scanner. In vitro tests using the ILMA indicated that the proposed design could be used to image target vessel walls with a spatial resolution of 313 μm at the frequency coding direction and more than 100 mm of longitudinal coverage. In vivo tests demonstrated that the images showed the vessel walls clearly by using the ILMA and also indicated that the ILMA could be used for small vessels. The proposed antenna may therefore be utilized to promote MR-based diagnoses and therapeutic solutions for cardiovascular atherosclerotic diseases. [Copyright &y& Elsevier]

Purpose: To evaluate the clinical implication of magnetic resonance imaging (MRI)-derived skeletal muscle index (SMI) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients undergoing induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) and further to develop a nomogram for predicting survival prognosis. Methods: SMI was determined through baseline MRI at the third cervical level. The nomogram was based on a training cohort involving 409 LANPC patients. We validated the prognostic accuracy of this prognostic model in an internal validation cohort (n = 204) and an external independent cohort (n = 272). Results: SMI was an independent risk factor for OS. A prognostic model comprising age, TNM stage and SMI for individual survival prediction was developed and graphically represented as a nomogram. The model showed favorable discrimination (C-index: 0.686), predictive accuracy [time dependent area under the curve (tAUC) at 5 years: 0.70], and calibration, and was further validated in the internal and external validation datasets. A risk stratification derived from the model stratified these patients into three prognostic subgroups with significantly different survival. Conclusions: Low SMI accessed by MRI was significantly associated with poor overall survival in LANPC patients undergoing IC + CCRT. Moreover, we established and validated a novel nomogram involving age, TNM stage and SMI that could provide accurate prognostic stratification among this population. [ABSTRACT FROM AUTHOR]

Large defects of frontal sinus (FS) might be difficult to manage effectively. Mismanagement of the large defects could lead to serious postoperative complications in anterior skull base surgery. This study introduces a simple and reliable method applying small supporting bone pieces to cover or insert into large FS defects, then the large defect of FS was transformed into the small defects which was sealed by bone wax successfully. Eleven patients underwent anterior skull base surgery for lesions or aneurysms, with the reconstruction of large FS defects by small supporting bone pieces. During craniotomy, mild violations of the FS mucosa were spared and sterilized, while severe violations required mucosal removal. Small supporting bone pieces were obtained from the inner plate of the bone flap and carefully covered or inserted into the large defects. The large defects were transformed into some small ones, which could be sealed effectively by bone wax. Demographic, intraoperative, and postoperative complication data were collected. Four patients had severe mucosal violations requiring removal, while 7 had mild violations sparing the mucosa. All underwent effective reconstruction with small supporting bone pieces. Median follow-up was 6 months. All cases showed effective FS morphology reconstruction, with no FS-related complications. Applying the small supporting bone pieces for large FS defect reconstruction can restore the FS morphology, preserve physiological function, and avoid postoperative complications. [ABSTRACT FROM AUTHOR]

IMB5036 is a novel pyridazinone compound with potent cytotoxicity. In this study, we reported its antitumour activity against pancreatic cancer and the underlying mechanism. We found that IMB5036 induced rapid cell swelling and increased membrane permeability in pancreatic cancer cells. IMB5036 increased the ratio of PI+ cells, which could be rescued by necroptosis inhibitor. Furthermore, MLKL inhibitor NSA attenuated the killing effect of IMB5036 on pancreatic cancer cells. IMB5036 stimulated translocation of MLKL and p‐MLKL from cytoplasm to cell membrane. IMB5036 upregulated the level of p‐RIPK1, p‐RIPK3, and p‐MLKL. At the same time, IMB5036 also partially activated apoptosis and pyroptosis. IMB5036 inhibited tumour growth in pancreatic xenograft. IMB5036 induced larger necrosis area, increased p‐MLKL level, and inhibited Ki67 expression in tumour mass. The study indicates that IMB5036 inhibits human pancreatic cancer growth primarily activating necroptosis. [ABSTRACT FROM AUTHOR]

Background: Portal vein system thrombosis (PVST) is a potentially fatal complication after splenectomy with esophagogastric devascularization (SED) in cirrhotic patients with portal hypertension. However, the impact of portal vein velocity (PVV) on PVST after SED remains unclear. Therefore, this study aims to explore this issue. Methods: Consecutive cirrhotic patients with portal hypertension who underwent SED at Tongji Hospital between January 2010 and June 2022 were enrolled. The patients were divided into two groups based on the presence or absence of PVST, which was assessed using ultrasound or computed tomography after the operation. PVV was measured by duplex Doppler ultrasound within one week before surgery. The independent risk factors for PVST were analyzed using univariate and multivariate logistic regression analysis. A nomogram based on these variables was developed and internally validated using 1000 bootstrap resamples. Results: A total of 562 cirrhotic patients with portal hypertension who underwent SED were included, and PVST occurred in 185 patients (32.9%). Multivariate logistic regression analysis showed that PVV was the strongest independent risk factor for PVST. The incidence of PVST was significantly higher in patients with PVV ≤ 16.5 cm/s than in those with PVV > 16.5 cm/s (76.2% vs. 8.5%, p < 0.0001). The PVV-based nomogram was internally validated and showed good performance (optimism-corrected c-statistic = 0.907). Decision curve and clinical impact curve analyses indicated that the nomogram provided a high clinical benefit. Conclusion: A nomogram based on PVV provided an excellent preoperative prediction of PVST after splenectomy with esophagogastric devascularization. [ABSTRACT FROM AUTHOR]

Asparagine synthetase is a key enzyme that catalyses the conversion of amide groups from glutamine or ammonium to aspartate, which leads to the generation of asparagine. However, the role of asparagine synthetase in plant immunity remains largely unknown. Here, we identified a Nicotiana benthamiana asparagine synthetase B (NbAS‐B) that associates with tomato mosaic virus coat protein‐interacting protein L (IP‐L) using the yeast two‐hybrid assay and examined its role in tobacco mosaic virus (TMV) resistance. The association of IP‐L with NbAS‐B was further confirmed by in vivo co‐immunoprecipitation, luciferase complementation imaging, and bimolecular fluorescence complementation assays. IP‐L and NbAS‐B interact in the nucleus and cytosol and IP‐L apparently stabilizes NbAS‐B, thus enhancing its accumulation. The expressions of IP‐L and NbAS‐B are continuously induced on TMV‐green fluorescent protein (GFP) infection. Co‐silencing of IP‐L and NbAS‐B facilitates TMV‐GFP infection. Overexpression of NbAS‐B in tobacco reduces TMV‐GFP infection by significantly improving the synthesis of asparagine. Furthermore, the external application of asparagine significantly inhibits the infection of TMV‐GFP by activating the salicylic acid signalling pathway. These findings hold the potential for the future application of asparagine in the control of TMV. [ABSTRACT FROM AUTHOR]

Background: CRF55_01B is a newly identified HIV-1 circulating recombinant form originated from MSM in China. However, its impact on the disease progression and transmission risk has not been investigated. This study aimed to determine the impact of CRF55_01B infection on viral dynamics and immunological status so as to provide scientific evidence for further control and prevention effort on CRF55_01B. Linear mixed effect models were applied to evaluate CD4 cell count decline and viral load increase by subtype. Results: Of the 3418 blood samples, 1446 (42.3%) were CRF07_BC, 1169 (34.2%) CRF01_AE, 467 (13.7%) CRF55_01B, 249 (7.3%) type B, and 87 (2.5%) other subtypes (CRF_08BC, CRF_01B, C). CRF55_01B had become the third predominant strain since 2012 in Shenzhen, China. CRF55_01B-infected MSM showed lower median of CD4 count than CRF07_BC-infected MSM (349.5 [IQR, 250.2–474.8] vs. 370.0 [IQR, 278.0–501.0], P < 0.05). CRF55_01B infection was associated with slower loss of CD4 count than CRF01_AE (13.6 vs. 23.3 [cells/µl]¹/²/year, P < 0.05)among MSM with initial CD4 count of 200–350 cells/µl. On the other hand, those infected with CRF55_01B showed higher median plasma HIV RNA load (5.4 [IQR, 5.0–5.9]) than both CRF01_AE (5.3 [IQR, 4.8–5.7], P < 0.05) and CRF07_BC (5.0 log10 [IQR, 4.5–5.5], P < 0.001) at the initiation of antiretroviral therapy. Furthermore, the annual increasing rate of viral load for CRF55_01B infection was significantly higher than that of CRF07_BC (2.0 vs. 0.7 log10 copies/ml/year, P < 0.01). Conclusions: The relatively lower CD4 count and faster increase of plasma HIV RNA load of CRF55_01B-infected MSM without antiretroviral therapy suggest that CRF55_01B may lead to longer asymptomatic phase and higher risk of HIV transmission. Strengthened surveillance, tailored prevention strategies and interventions, and in-depth research focusing on CRF55_01B are urgently needed to forestall potential epidemic. [ABSTRACT FROM AUTHOR]

Simple Summary: Plasma Epstein–Barr virus (EBV) DNA is an important prognostic marker for nasopharyngeal carcinoma (NPC). However, EBV DNA is less sensitive to locoregional recurrence compared to distant metastasis in NPC. Numerous findings suggest that the presence of tumour-infiltrating lymphocytes (TILs) is associated with NPC prognosis. Nevertheless, NPC is characterised by the presence of abundant TILs. This study aims to generate TIL scores in NPC from H&E-stained tissue slide images for NPC prognosis. We employed artificial intelligence and deep learning-based method for generating TIL score. Our results indicate that our methods have strong prognostic value compared to the EBV DNA copies in locoregional recurrence cases. Background: Locoregional recurrence of nasopharyngeal carcinoma (NPC) occurs in 10% to 50% of cases following primary treatment. However, the current main prognostic markers for NPC, both stage and plasma Epstein–Barr virus DNA, are not sensitive to locoregional recurrence. Methods: We gathered 385 whole-slide images (WSIs) from haematoxylin and eosin (H&E)-stained NPC sections (n = 367 cases), which were collected from Sun Yat-sen University Cancer Centre. We developed a deep learning algorithm to detect tumour nuclei and lymphocyte nuclei in WSIs, followed by density-based clustering to quantify the tumour-infiltrating lymphocytes (TILs) into 12 scores. The Random Survival Forest model was then trained on the TILs to generate risk score. Results: Based on Kaplan–Meier analysis, the proposed methods were able to stratify low- and high-risk NPC cases in a validation set of locoregional recurrence with a statically significant result (p < 0.001). This finding was also found in distant metastasis-free survival (p < 0.001), progression-free survival (p < 0.001), and regional recurrence-free survival (p < 0.05). Furthermore, in both univariate analysis (HR: 1.58, CI: 1.13–2.19, p < 0.05) and multivariate analysis (HR:1.59, CI: 1.11–2.28, p < 0.05), we also found that our methods demonstrated a strong prognostic value for locoregional recurrence. Conclusion: The proposed novel digital markers could potentially be utilised to assist treatment decisions in cases of NPC. [ABSTRACT FROM AUTHOR]

Using a new synthesis method, we have prepared two different coordination configurations of chiral cyclometalated N^C^N-coordinated and C^N-coordinated Pt(II) complexes by controlling the Cl− source. Single-crystal X-ray diffraction determines the tridentate and bidentate structures. All N^C^N-coordinated and C^N-coordinated Pt(II) complexes emit green-yellow light in CH 2 Cl 2 solutions. Square-planar N^C^N-Coordinated complexes (−)- 1 and (−)- 2 show remarkable aggregation-induced emission behaviors in mixed CH 2 Cl 2 / n -hexane solutions with the emission quantum yield (Φ em) intensified significantly. In addition, the luminescent color could change from green-yellow to red by varying the volumetric fraction of n -hexane. Complex (−)- 2 grafted with long alkyl chains could form helical stacking aggregates, inducing enhanced ECD signals and measurable CPL activity. The yellow and orange solids of complex (−)- 1 can be separated, and a high-contrast mechanochromic luminescence is found for the yellow form. Furthermore, the potential utility has been attempted in anti-counterfeiting applications based on the yellow solid of (−)- 1. This study provides a new design strategy for the preparation of chiral cyclometalated Pt(II) complexes with specific configurations and aggregated forms that have various optical and electronic properties. [Display omitted] • Two different coordination configurations of chiral Pt(II) complexes have been prepared by controlling the Cl− source. • Square-planar complexes (−)- 1 and (−)- 2 show remarkable aggregation-induced emission behaviors. • Complex (−)- 1 exhibits attractive mechanochromic luminescence. • Square-planar complex (−)- 2 generates helical assembled architectures, resulting in enhanced chiroptical signals. [ABSTRACT FROM AUTHOR]

Alternative splicing is an important basic mechanism for eukaryotes to control gene expression. Different forms of alternative splicing may lead to the production of protein subtypes with different functions, leading to the expansion of protein diversity in organisms, affecting cell production and metabolism, and is even related to the occurrence of many diseases. Many studies have shown that ferritin is usually associated with inflammation, vascular proliferation, and tumors, which is the focus of immunological research. It not only plays a role in iron metabolism and storage in the body, but also plays an important regulatory role in pathways related to immune and inflammatory regulation. However, there are few studies on alternative splicing events of the ferritin gene nowadays. Therefore, this study identified three different splicing isoforms in its ferritin gene fthl27 of Miichthys miiuy through Sanger sequencing, qRT-PCR, and other experimental techniques, and we found that three different splicing isoforms of the ferritin gene fthl27 in M. Miiuy cells showed an upregulation trend after being stimulated by Lipopolysaccharide (LPS) and poly (I: C). The experiment also found that the three isoforms may have different regulatory effects on the expression of inflammatory factors and antiviral immune factors, playing an important role in the innate immune response of fish. • Three alternative splicing isoforms of the fthl27 gene were identified in miiuy croaker. • Three isoforms of fthl27 activate the expression of Inflammatory factor. • All three isoforms of fthl27 may be involved in innate immunity. [ABSTRACT FROM AUTHOR]

Endophytic bacteria, which are common in plant tissues, may help to control plant pathogens and enhance plant growth. Camellia oleifera, an oil-producing plant, is widely grown in warm, subtropical, hilly regions in China. However, C. oleifera is strongly negatively affected by C. oleifera anthracnose, which is caused by Colletetrichum fructicola. To find a suitable biocontrol agent for C. oleifera anthracnose, 41 endophytes were isolated from the stems, leaves, and roots of C. oleifera. Bacterial cultures were identified based on analyses of 16S rDNA sequences; most strains belonged to the genus Bacillus. The antagonistic effects of these strains on C. fructicola were tested in vitro. In total, 16 strains inhibited C. fructicola growth, with B. subtilis strain 1-L-29 being the most efficient. Strain 1-L-29 demonstrated antagonistic activity against C. siamense, C. asianum, Fusarium proliferatum, Agaricodochium camellia, and Pseudomonas syringae. In addition, this strain produced indole acetic acid, solubilized phosphate, grew on N-free media, and produced siderophores. To facilitate further microecological studies of this strain, a rifampicin-resistant, green fluorescent protein (GFP)-labeled strain, 1-L-29gfpr, was created using protoplast transformation. This plasmid had good segregational stability. Strain 1-L-29gfpr was re-introduced into C. oleifera and successfully colonized root, stem, and leaf tissues. This strain remained at a stable concentration in the root more than 20 d after inoculation. Fluorescence microscopic analysis showed that strain 1-L-29gfpr thoroughly colonized the root surfaces of C. fructicola as well as the root vascular tissues of Arabidopsis thaliana. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively investigate the optimal regimen of concurrent chemotherapy for nasopharyngeal carcinoma (NPC) by comparing clinical outcomes of patients who received platinum-based and non-platinum-based concurrent chemoradiotherapy (CCRT) regimens.Methods: Based on a prospectively maintained database from 1998 to 2013 in an endemic area, a total of 4608 newly diagnosed, biopsy-proven, and non-disseminated NPC patients were identified and allocated into three cohorts based on concurrent chemotherapy regimens: cisplatin-based (CP) chemotherapy cohort, other platinum-based (OP) chemotherapy cohort, and non-platinum-based (NP) chemotherapy cohort. Overall survival (OS) and disease-free survival (DFS) were estimated using the Cox proportional hazards model and propensity score analysis of treatment using an inverse probability weighting model (PSA/IPTW). Finally, sensitivity analysis estimated the effects of potential unmeasured confounders.Results: The median follow-up time was 68.5 months (range 2-194 months). The multivariate Cox model showed that NP regimens were significantly related with worse survival compared with CP or OP regimens (OS: HR 1.51, 95% CI 1.16-2.00, P = 0.002; HR 1.68, 95% CI 1.24-2.27, P = 0.001; DFS: HR 1.31, 95% CI 1.03-1.66, P = 0.031; HR 1.50, 95% CI 1.14-1.97, P = 0.004, respectively). Meanwhile, no significant survival difference was found between OP and CP regimens. The PSA/IPTW method, CCRT-specific and III-IVB NPC cohort subgroup analysis showed similar results. Sensitivity analysis confirmed the robustness of our results.Conclusions: Platinum-based concurrent chemotherapy, including both CP and OP regimens, yields better survival benefits for non-metastatic NPC patients than the NP regimen and remains the optimal regimen for these patients. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the incidence, consequences, and predictors of serious chemotherapy‐induced thrombocytopenia (CIT) in nasopharyngeal carcinoma (NPC). Materials and Methods: We retrospectively reviewed the clinical records of patients with NPC between 2013 and 2015. Multivariate Cox proportional hazards regression model and propensity score matching were used to estimate the effect of serious CIT on overall survival. Univariate and multivariate logistic regression analyses were applied to identify the predictors of serious CIT. Results and Conclusion: The incidence of serious CIT was 5.21% in patients with NPC. Patients who experienced serious thrombocytopenia had a worse long‐term prognosis, while the difference in short‐term survival rate was slight. Chemotherapy regimens of gemcitabine and platinum, 5‐fluorouracil and platinum, taxane and platinum, serum potassium ion concentration, serum lactate dehydrogenase levels, platelet count, red blood cell count, and estimated glomerular filtration rate were predictors of serious CIT. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of lipid metabolism is closely associated with cancer progression. The study aimed to establish a prognostic model to predict distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC), based on lipidomics. Methods: The plasma lipid profiles of 179 patients with locoregionally advanced NPC (LANPC) were measured and quantified using widely targeted quantitative lipidomics. Then, patients were randomly split into the training (125 patients, 69.8%) and validation (54 patients, 30.2%) sets. To identify distant metastasis-associated lipids, univariate Cox regression was applied to the training set (P < 0.05). A deep survival method called DeepSurv was employed to develop a proposed model based on significant lipid species (P < 0.01) and clinical biomarkers to predict DMFS. Concordance index and receiver operating curve analyses were performed to assess model effectiveness. The study also explored the potential role of lipid alterations in the prognosis of NPC. Results: Forty lipids were recognized as distant metastasis-associated (P < 0.05) by univariate Cox regression. The concordance indices of the proposed model were 0.764 (95% confidence interval (CI), 0.682–0.846) and 0.760 (95% CI, 0.649–0.871) in the training and validation sets, respectively. High-risk patients had poorer 5-year DMFS compared with low-risk patients (Hazard ratio, 26.18; 95% CI, 3.52–194.80; P < 0.0001). Moreover, the six lipids were significantly correlated with immunity- and inflammation-associated biomarkers and were mainly enriched in metabolic pathways. Conclusions: Widely targeted quantitative lipidomics reveals plasma lipid predictors for LANPC, the prognostic model based on that demonstrated superior performance in predicting metastasis in LANPC patients. [ABSTRACT FROM AUTHOR]

Developing multifunctional materials for 2-naphthol (2-NAP) monitoring is in urgent demand since 2-NAP not only brings us convenience but also causes serious environmental and health issues. Herein, we report a novel β-cyclodextrin (β-CD)-based molecular-responsive photonic hydrogel chemosensor composed of a poly(N-isopropylacrylamide-co-maleic anhydride-β-cyclodextrin) (PNACD) hydrogel with embedded superparamagnetic Fe3O4 colloidal particle chains, for highly sensitive and visual detection of 2-NAP in aqueous solution. The Fe3O4 particle chains in the polymer matrix could strongly diffract visible light and transmit a 2-NAP concentration signal to the color change of the gel by changing the gel volume and lattice spacing of Fe3O4 particles. The rich β-CD groups attached to the polymer networks could specifically recognize and bind to 2-NAP by forming stable β-CD/2-NAP inclusion complexes. This specific molecular recognition expanded the gel, increased the particle spacing, and thus redshifted the reflection wavelengths of the gel and indicated the color changes of the gel. This photonic hydrogel exhibited remarkable thermo- and pH-dependent responsiveness to 2-NAP, a wider linear detection range of 0.01–500 μM and a comparatively lower detection concentration of 0.01 μM compared with the conventional instrument-based methods. Besides, it also demonstrated excellent regenerability and was applicable to monitor 2-NAP in a simulated contaminated river water sample. Such a multifunctional hydrogel with high sensitivity and selectivity toward 2-NAP as well as excellent recyclability holds great potential in sensitive, precise and naked-eye detection of aromatic pollutants in contaminated water bodies. [ABSTRACT FROM AUTHOR]

Purpose: The efficacy and safety of nimotuzumab (NTZ) added to concurrent chemoradiotherapy (CCRT) were investigated in patients with stage III–IVa nasopharyngeal carcinoma (NPC). Methods: Patients with stage III–IVa NPC treated with CCRT, with or without NTZ, were screened between January 2015 and December 2017. We compared patients' overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) between different therapeutic regimens. Propensity score matching (PSM) was applied to reduce the selection bias. Nomogram models were developed to predict the survival of CCRT with or without NTZ. Results: Four hundred and twenty-six patients were included after PSM, with 213 patients in each regimen. Compared with NPC patients receiving CCRT alone, patients who received NTZ plus CCRT treatment had significantly better OS (5 year OS, 76.1 vs. 72.3%, P = 0.004), PFS (5 year PFS, 73.2 vs. 69.0%, P = 0.002), and LRFS (5 year LRFS, 73.2 vs. 69.0%, P = 0.028). A multivariate Cox regression analysis demonstrated that, compared with receiving CCRT alone, NTZ plus CCRT was an independently positive factor for OS, PFS, and LRFS. No significant difference was observed in the major toxicities between the two treatments (all P > 0.05). In addition, the nomogram presented good accuracy for predicting the prognosis of NPC patients. Conclusion: CCRT combined with NTZ presented favorable clinical outcomes for stage III–IVa NPC patients with good tolerance and similar toxicity compared to CCRT alone. A prospective, randomized clinical trial is essential to validate the current findings. [ABSTRACT FROM AUTHOR]

Background: To develop and validate a predictive nomogram for tumor residue 3–6 months after treatment based on postradiotherapy plasma Epstein–Barr virus (EBV) deoxyribonucleic acid (DNA), clinical stage, and radiotherapy (RT) dose in patients with stage II–IVA nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods: In this retrospective study, 1050 eligible patients with stage II–IVA NPC, who completed curative IMRT and underwent pretreatment and postradiotherapy (-7 to +28 days after IMRT) EBV DNA testing, were enrolled from 2012 to 2017. The prognostic value of the residue was explored using Cox regression analysis in patients (n=1050). A nomogram for predicting tumor residues after 3–6 months was developed using logistic regression analyses in the development cohort (n=736) and validated in an internal cohort (n=314). Results: Tumor residue was an independent inferior prognostic factor for 5-year overall survival, progression-free survival, locoregional recurrence-free survival and distant metastasis-free survival (all P<0.001). A prediction nomogram based on postradiotherapy plasma EBV DNA level (0 vs. 1–499 vs. ≥500 copies/ml), clinical stage (II vs. III vs. IVA), and RT dose (68.00–69.96 vs. 70.00–74.00 Gy) estimated the probability of residue development. The nomogram showed better discrimination (area under the curve (AUC): 0.752) than either the clinical stage (0.659) or postradiotherapy EBV DNA level (0.627) alone in the development and validation cohorts (AUC: 0.728). Conclusions: We developed and validated a nomogram model integrating clinical characteristics at the end of IMRT for predicting whether tumor will residue or not after 3–6 months. Thus, high-risk NPC patients who might benefit from immediate additional intervention could be identified by the model, and the probability of residue can be reduced in the future. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the value of a serum metabolomics-based metabolic signature for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, thereby assisting clinical decisions. Methods: In this retrospective study, a total of 320 LA-NPC patients were randomly divided into a training set (ca. 70%; n = 224) and a validation set (ca. 30%; n = 96). Serum samples were analyzed using widely targeted metabolomics. Univariate and multivariate Cox regression analyses were used to identify candidate metabolites related to progression-free survival (PFS). Patients were categorized into high-risk and low-risk groups based on the median metabolic risk score (Met score), and the PFS difference between the two groups was compared using Kaplan–Meier curves. The predictive performance of the metabolic signature was evaluated using the concordance index (C-index) and the time-dependent receiver operating characteristic (ROC), and a comprehensive nomogram was constructed using the Met score and other clinical factors. Results: Nine metabolites were screened to build the metabolic signature and generate the Met score, which effectively separated patients into low- and high-risk groups. The C-index in the training and validation sets was 0.71 and 0.73, respectively. The 5-year PFS was 53.7% (95% CI, 45.12–63.86) in the high-risk group and 83.0% (95%CI, 76.31–90.26) in the low-risk group. During the construction of the nomogram, Met score, clinical stage, pre-treatment EBV DNA level, and gender were identified as independent prognostic factors for PFS. The predictive performance of the comprehensive model was better than that of the traditional model. Conclusion: The metabolic signature developed through serum metabolomics is a reliable prognostic indicator of PFS in LA-NPC patients and has important clinical significance. [ABSTRACT FROM AUTHOR]

Mutations in the COL4A5 gene result in X-linked Alport syndrome, homozygous or compound heterozygous mutations in COL4A3 or COL4A4 are responsible for autosomal recessive Alport syndrome, and heterozygous mutations in COL4A3 or COL4A4 cause autosomal dominant Alport syndrome or benign familial hematuria. Recently, the existence of a digenic inheritance in Alport syndrome has been demonstrated. We here report heterozygous COL4A3 and COL4A4 digenic mutations in cis responsible for benign familial hematuria. Using bioinformatics analyses and pedigree verification, we showed that COL4A4 c.1471C>T and COL4A3 c.3418 + 1G>T variants in cis are pathogenic and co-segregate with the benign familial hematuria. This result suggests that COL4A3 and COL4A4 digenic mutations in cis mimicking an autosomal dominant inheritance should be considered as a novel inheritance pattern of benign familial hematuria, although the disease-causing mechanism remains unknown. [ABSTRACT FROM AUTHOR]

Background: The serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte (P/MII) ratio might be a more predictable indicator of pregnancy and neonatal outcomes as compare to P/estradiol (E2) or P alone. Hence, we conducted a larger population study to compare the pregnancy and neonatal outcomes in the low and high P/MII ratio. Methods: A retrospective, single-center, larger population cohort study between January 2015 and August 2021. Calculate the threshold effect of P/MII ratio on clinical pregnancy rate according to the construct smooth curve fitting. Divide data into two groups by threshold for comparison. Results: 3566 fresh ICSI-ET cycles were included, in which 929 singleton delivery and 676 twin deliveries. Compare to P/MII ≤ 0.367 group, it indicated that the P/MII > 0.367 group had a lower clinical pregnancy rate and live birth rate, furthermore, a significantly higher rate of LBW and SGA were observed in the singleton and twin deliveries. No deleterious impact of high P/MII ratio on embryo quality and undesirable pregnancy outcomes was shown. Conclusions: When P/MII is higher than 0.367, may have adverse impacts on pregnancy and neonatal outcomes for ICSI cycle. [ABSTRACT FROM AUTHOR]

Background: To explore the short‐ and long‐term outcomes in patients with nasopharyngeal carcinoma (NPC) with magnetic resonance imaging (MRI)‐detected residual disease at 3 months post‐treatment who received intervention either promptly (0 month) or following observation (after an additional 3 months). Methods: A total of 272 patients with residual disease at 3 months post‐treatment (observation [observation for additional 3 months]: 122, intervention [prompt intervention]: 150) were analyzed. Univariate and multivariate analyses were performed to examine the survival. Adverse events were analyzed in all patients. Results: Patients in the observation group had a lower 3‐year overall survival (77.1% vs. 85.2%), progression‐free survival (10.2% vs. 18.1%), and locoregional relapse‐free survival (10.2% vs. 20.6%) (all p <.05), but not distant metastasis‐free survival (83.8% vs. 78.4%, p =.189), whereas patients in the intervention group achieved higher complete remission (CR) rates (43.3% vs. 21.2%, p =.003). Patients who achieved CR after prompt intervention had a better survival rate than those who achieved observation‐CR or non‐CR (p <.001). Multivariate analyses revealed that a wait‐and‐see policy was an independent prognostic factor for impaired survival (p <.001). No significant differences of acute or late toxicities were observed between the two groups. Conclusions: Patients with NPC with MRI‐detected residual disease 3 months post‐radiotherapy should be encouraged to undergo prompt intervention rather than adopting a passive wait‐and‐see policy. [ABSTRACT FROM AUTHOR]

Background Whether the waiting time for radical radiotherapy (WRT) detrimentally impacts nasopharyngeal carcinoma (NPC) prognosis is unclear. We estimated the influence of WRT on overall survival (OS) and disease-specific survival (DSS) of NPC. Patients and methods Patients were identified from prospectively maintained database. WRT was calculated from histological diagnosis to initiation of radiotherapy (RT). Survival analysis was estimated using Weibull parametric model and propensity score analysis (PSA). Recursive partitioning analysis (RPA) identified optimal WRT threshold via conditional inference trees to estimate the greatest survival differences based on randomly selected training and validation sets, and this process was repeated 1000 times to ensure threshold robustness. Sensitivity analysis estimated effects of potential unmeasured confounders. Results A total of 9896 patients were included. In multivariate analysis, WRT of 31–60°d, of 61–90°d and of greater than 90°d independently increased mortality risk compared to less than 30°d. Upon RPA, ranges of 30–35°d with the peak of 30°d were confirmed with 89% of simulations validating optimal thresholds. In threshold-based groups, adjusted hazard ratios (HRs) for WRT of greater than 30°d by both Weibull model and PSA were significantly higher than for WRT of less than 30°d [OS: HR = 1.13, 95% confidence interval (CI) 1.04–1.23, P = 0.003; DSS: HR = 1.15, 95% CI 1.05–1.26, P = 0.002]. Sensitivity analysis revealed robustness of results. Conclusions WRT independently affects survival. Increasing WRT beyond 30°d was most consistently detrimental to survival. WRT of NPC should be as short as reasonably achievable (ASARA). [ABSTRACT FROM AUTHOR]

Antibiotics are widely used for treating bacterial infections. However, excessive or improper use of antibiotics can pose a serious threat to human health and water environments, and thus, developing cost-effective, portable and effective strategies to analyze and detect antibiotics is highly desired. Herein, we reported a responsive photonic hydrogel (RPH)-based optical biosensor (PPNAH) with superior recyclability for sensitive and colorimetric determination of a typical β -lactam antibiotic penicillin G (PG) in water. This sensor was composed of poly(N -isopropylacrylamide- co -acrylamide) smart hydrogel with incorporated penicillinase and Fe 3 O 4 @SiO 2 colloidal photonic crystals (CPCs). The sensor could translate PG concentration signals into changes in the diffraction wavelength and structural color of the hydrogel. It possessed high sensitivity and selectivity to PG and excellent detection performances for other two typical β -lactam antibiotics. Most importantly, due to the unique thermosensitivity of the poly(N -isopropylacrylamide) moieties in the hydrogel, the PG-responded PPNAH sensor could be facilely regenerated via a simple physical method at least fifty times while without compromising its response performance. Besides, our sensor was suitable for monitoring the PG-contaminated environmental water and displayed satisfactory detection performances. Such a sensor possessed obvious advantages of superior recyclability, highly chemical stability, low production cost, easy fabrication, wide range of visual detection, simple and intuitive operation for PG detection, and environmental-friendliness, which holds great potential in sensitive and colorimetric detection of the PG residues in polluted water. [ABSTRACT FROM AUTHOR]