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Zai-Quan Dong,1,* Xi-Rong Li,2,* Lin He,3,4 Guang He,3,4 Tao Yu,3,4 Xue-Li Sun1 1Psychological Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 2Mental Health Center, First Affiliated Hospital, Chongqing Medical University, Chongqing, 3Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 4Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Objective: Genetic variabilities within the serotoninergic system may predict response or remission to antidepressant drugs. Several serotonin receptor (5-HTR) gene polymorphisms have been associated with susceptibility to psychiatric diseases. In this study, we analyzed the correlation between 5-HTR1A and 5-HTR2A polymorphisms and response or remission to selective serotonin reuptake inhibitors (SSRIs) drugs. Methods: Two hundred and ninety patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder were involved in this study. SSRIs (fluoxetine, paroxetine, citalopram, or sertraline) were selected randomly for treatment. The Hamilton Rating Scale for Depression was used to evaluate the antidepressant effect. To assess 5-HTR gene variabilities, two single-nucleotide polymorphisms in 5-HTR1A (rs1364043 and rs10042486) and three in 5-HTR2A (rs6311, rs6313, and rs17289304) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the Sequenom MassARRAY Analyzer 4 system. Results: There were 220 responders and 70 nonresponders (120 remissioners and 170 nonremissioners) after 6 weeks of treatment. We found no association between any of the five 5-HTR1A and 5-HTR2A gene polymorphisms and antidepressant drug response or remission (P>0.05). It is worth mentioning that TT genotype frequency of rs10042486 was significantly different from the CT genotype frequency between responders and nonresponders, although the significance was not maintained after correcting for multiple testing. Conclusion: Thus, 5-HTR1A and 5-HTR2A gene polymorphisms may not play an important role in antidepressant drug response or remission. Keywords: genetic association, major depressive disorder, SSRIs

To investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its effects on angiogenesis and lymphangiogenesis in oral carcinoma. Immunohistochemistry was used to study the expression of CEACAM1, LYVE1 and CD31, double-labelling immunofluorescence was used to detect the co-expression of CEACAM1 and LYVE1, and double-labelling immunohistochemistry was performed to observe the co-expression of LYVE1 and CD31 in vessels. Membranous CEACAM1 was expressed in well-differentiated squamous cell carcinoma and cytoplastic CEACAM1 in poorly and moderately differentiated carcinoma (P<0.05). More CEACAM1-positive vessels were observed in CEACAM1-positive tumors with cytoplasmic expression than with membranous expression (P<0.001). Co-expression of CEACAM1 and LYVE1, LYVE1 and CD31 in vessels was more common in CEACAM1-positive tumors with cytoplasmic expression than with membranous expression (P<0.001). CEACAM1 has different distribution in oral carcinoma. Membranous CEACAM1 inhibits angiogenesis and lymphangiogenesis, but cytoplasmic CEACAM1 promotes angiogenesis, and even promotes lymphangiogenesis by mediating the transformation of vascular endothelial cells (VECs) into lymphatic endothelial cells (LECs). [ABSTRACT FROM AUTHOR]

Background: Acute aortic dissection (AD) in pregnancy poses a lethal risk to both mother and fetus. However, well-established therapeutic guidelines are lacking. This study aimed to investigate clinical features, outcomes and optimal management strategies for pregnancy-related AD., Methods: We conducted a retrospective multicentre cohort study including 67 women with acute AD during pregnancy or within 12 weeks postpartum from three major cardiovascular centres in China between 2003 and 2021. Patient characteristics, management strategies and short-term outcomes were analysed., Results: Median age was 31 years, with AD onset at median 32 weeks gestation. Forty-six patients (68.7%) had type A AD, of which 41 underwent immediate surgery. Overall maternal mortality was 10.4% (7/67) and fetal mortality was 26.9% (18/67). Compared with immediate surgery, selective surgery was associated with higher risk of composite maternal and fetal death (adjusted RR: 12.47 (95% CI 3.26 to 47.73); p=0.0002) and fetal death (adjusted RR: 8.77 (95% CI 2.33 to 33.09); p=0.001)., Conclusions: Immediate aortic surgery should be considered for type A AD at any stage of pregnancy or postpartum. For pregnant women with AD before fetal viability, surgical treatment with the fetus in utero should be considered. Management strategies should account for dissection type, gestational age, and fetal viability., Trial Registration Number: NCT05501145., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background. The interplay among human gut microbiota (GM) composition, osteoarthritis (OA) and OA-related medication use has been extensively discussed. However, to date, there has been no exploration of the genetic correlation among these three factors. Hypothesis/Gap. The potential causal link between GM and OA), and whether medications influence this relationship, remains unclear. Methods. We utilized bidirectional Mendelian randomization (MR) to explore the genetic associations between GM and OA. We leveraged genome-wide association study (GWAS) summary statistics from the MiBioGen and GO consortia, which provided data on GM taxa and OA cases, respectively. We identified outlier single-nucleotide polymorphisms using radial-MR and assessed causal associations using inverse variance weighting (IVW), weighted median and MR-Egger methods. Robust outcomes, consistent across these methods, were reported. We addressed potential biases through tests for horizontal pleiotropy and heterogeneity, supplemented by the Mendelian randomization pleiotropy residual sum and outlier method. Multivariable MR techniques were applied to adjust for OA medication use using UK Biobank data. Results. IVW estimates revealed a significant increase in hip OA risk for Gordonibacter and Eubacterium (brachy group) [odds ratio (OR): 1.09, 95% confidence interval (CI): 1.04-1.15, P =7.82E-04; OR: 1.09, 95% CI: 1.03-1.16, P =4.67E-03, respectively]. Conversely, Senegalimassilia , Slackia and Streptococcus exhibited protective effects (OR: 0.88, P =2.14E-02; OR: 0.88, P =3.33E-02; 0.91, P =4.29E-02). Sutterella increased the risk of knee OA (OR=1.15, 95% CI: 1.07-1.25, P =4.06E-04), while Haemophilus decreased it (OR=0.94, 95% CI: 0.88-1.00, P =4.26E-02). No significant heterogeneity or horizontal pleiotropy was observed in the results. Even after accounting for the potential confounding effect of medication, the results remained consistent. No reverse causation was detected. Conclusions. Our MR study reveals gut microbiome links to OA risk. Associations hold after adjusting for medication, indicating a potential causal connection between GM and OA.

The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-β. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Viral diseases pose a significant threat to livestock husbandry and plant cultivation. CRISPR/Cas9-mediated targeted editing of viral genes offers a promising approach to antiviral therapy. The silkworm, Bombyx mori, is an economically important insect susceptible to infection by B. mori nucleopolyhedrovirus (BmNPV), and viral outbreaks cause severe economic losses to the sericulture industry. Here, we identified BmNPV orf76 as a viral late gene that is highly similar to Autographa californica multiple nucleopolyhedrovirus Ac93. The deletion of orf76 abolished BmNPV proliferation and hindered the production of infectious budded viruses. We generated a transgenic line, Cas9(+)/sgorf76(+), that did not affect the growth or development of the silkworm and demonstrated that the transgenic line Cas9(+)/sgorf76(+) efficiently cleaved orf76 at the sgorf76 site, resulting in large deletions at 120 h post-infection, with no observed off-target effects. Survival analyses revealed that the transgenic line Cas9(+)/sgorf76(+) exhibited significantly higher survival rates than the control lines Cas9(-)/sgorf76(-), regardless of the BmNPV inoculation dose. Additionally, the number of BmNPV DNA copies and the expression levels of viral genes were markedly inhibited in the transgenic line Cas9(+)/sgorf76(+) compared with the control line Cas9(-)/sgorf76(-). The results provide a promising target for Cas9-mediated antiviral therapy against BmNPV, and the findings provide new insights for baculovirus gene function studies and lepidopteran pest control., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ginseng Radix et Rhizoma is a unique traditional Chinese herbal medicine in China, with a long medicinal history, unique healthcare effects, and a profound cultural value. The development of the Ginseng Radix et Rhizoma industry has practical and symbolic significance for the traditional Chinese medicine(TCM) industry. Under the new situation, China's Ginseng Radix et Rhizoma industry has faced new development opportunities and also internal and external challenges. It is urgent to deeply analyze the practical problems and explore the solutions. This article systematically reviews the current situation of China's Ginseng Radix et Rhizoma industry from the industrial chain and analyzes the current problems and development trends of this industry, aiming to provide reference and a decision-making basis for the high-quality development of this industry.

Background: Bombyx mori nuclear polyhedrosis virus (BmNPV), as a typical baculovirus, is the primary pathogen that infects the silkworm B. mori, a lepidopteran species. Owing to the high biological safety of BmNPV in infecting insects, it is commonly utilized as a biological insecticide for pest control. Apoptosis is important in the interaction between the host and pathogenic microorganisms. MicroRNAs (miRNAs) influence immune responses and promote stability of the immune system via apoptosis. Therefore, the study of apoptosis-related miRNA in silkworms during virus infection can not only provide support for standardizing the prevention and control of diseases and insect pests, but also reduce the economic losses to sericulture caused by the misuse of biological pesticides., Results: Through transcriptome sequencing, we identified a miRNA, miR-31-5p, and demonstrated that it can inhibit apoptosis in silkworm cells and promote the proliferation of BmNPV in BmE-SWU1 cells. We identified a target gene of miR-31-5p, B. mori cytochrome P450 9e2 (BmCYP9e2), and demonstrated that it can promote apoptosis in silkworm cells and inhibit the proliferation of BmNPV. Moreover, we constructed transgenic silkworm strains with miR-31-5p knockout and confirmed that they can inhibit the proliferation of BmNPV., Conclusion: These data indicate that miR-31-5p may exert functions of inhibiting apoptosis and promoting virus proliferation by regulating BmCYP9e2. The findings demonstrate how miRNAs influence host cell apoptosis and how they are involved in the host immune system response to viruses, providing important insights into the applications of biological insecticides for pest control. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The boom in cancer immunotherapy has provided many patients with a better chance of survival, but opportunities often come with challenges. Single immunotherapy is not good enough to eradicate tumours, and often fails to achieve the desired therapeutic effect because of the low targeting of immunotherapy drugs, and causes more side effects. As a solution to this problem, researchers have developed several nano Drug Delivery Systems (NDDS) to deliver immunotherapeutic agents to achieve good therapeutic outcomes. However, traditional drug delivery systems (DDS) have disadvantages such as poor bioavailability, high cytotoxicity, and difficulty in synthesis, etc. Herbal Polysaccharides (HPS), derived from natural Chinese herbs, inherently possess low toxicity. Furthermore, the biocompatibility, biodegradability, hydrophilicity, ease of modification, and immunomodulatory activities of HPS offer unique advantages in substituting traditional DDS. This review initially addresses the current developments and challenges in immunotherapy. Subsequently, it focuses on the immunomodulatory mechanisms of HPS and their design as nanomedicines for targeted drug delivery in tumour immunotherapy. Our findings reveal that HPS-based nanomedicines exhibit significant potential in enhancing the efficacy of cancer immunotherapy, providing crucial theoretical foundations and practical guidelines for future clinical applications.

Background: Chemotherapy-induced peripheral neuropathy not only affects the tolerability of chemotherapy, but also causes intolerable and prolonged neuropathic pain in cancer patients. Currently, duloxetine is the only drug used to treat chemotherapy-induced peripheral neuropathy. However, the clinical use of this drug still faces several challenges. Therefore, we focused on traditional Chinese medicine to find an effective and safe alternative medicine. Huangqi Guizhi Wuwu Decoction is a traditional Chinese medicine that has been clinically used for treating nerve pain for thousands of years. This study aimed to investigate the neuroprotective effect of Huangqi Guizhi Wuwu Decoction on cisplatin-induced nerve injury in PC12 cells and to elucidate its potential mechanism of action., Methods: Huangqi Guizhi Wuwu Decoction-containing serum and blank serum were prepared from a rat model. The protective effects of Huangqi Guizhi Wuwu Decoction on cisplatin (10 µmol/L)-induced PC12 cell injury were assessed by a Cell Counting Kit-8 assay. RNA expression in Huangqi Guizhi Wuwu Decoction-protected PC12 cells was analyzed using RNA-seq, and subsequently, differentially expressed genes were further analyzed using Gene Ontology and Gene Set Enrichment Analysis., Results: The Cell Counting Kit-8 results showed that pretreatment of PC12 cells with Huangqi Guizhi Wuwu Decoction-containing serum (5%, 10%, 15%) significantly increased cells' viability to 10 µmol/L cisplatin-induced cell death. RNA-seq analysis revealed 843 differentially expressed genes in the chemotherapy-induced peripheral neuropathy group and 249 in the Huangqi Guizhi Wuwu Decoction group. The gene set enrichment analysis results in this study suggest that Huangqi Guizhi Wuwu Decoction may treat chemotherapy-induced peripheral neuropathy by enhancing axon guidance., Conclusions: This study provides valuable evidence for using Huangqi Guizhi Wuwu Decoction in treating chemotherapy-induced peripheral neuropathy, partially achieved by improving axon guidance pathways.

The 871C silkworm strain exhibits a high level of resistance to Bombyx mori nucleopolyhedrovirus (BmNPV), making it a valuable variety for the sericulture industry. Understanding the underlying mechanism of its resistance holds great biological significance and economic value in addressing viral disease risks in sericulture. Initially, we infected the resistant strain 871C and its control strain 871 with BmNPV and conducted secondary infection experiments using the progeny occlusion bodies (OBs). As a result, a significant decrease in pathogenicity was observed. Electron microscopy analysis revealed that 871C produces progeny virions with defective DNA packaging, reducing virulence following BmNPV infection. Blood proteomic identification of the silkworm variety 871C and control 871 after BmNPV infection demonstrated the crucial role of the viral proteins P6.9 and VLF-1 in the production of defective viruses by impeding the proper encapsulation of viral DNA. Additionally, we discovered that BmHSP19.9 interacts with P6.9 and VLF-1 and that its expression is significantly upregulated after BmNPV infection. BmHSP19.9 exhibits strong antiviral activity, in part by preventing the entry of the proteins P6.9 and VLF-1 into the nucleus, thereby hindering viral nucleocapsid and viral DNA assembly. Our findings indicate that the antiviral silkworm strain 871C inhibits BmNPV proliferation by upregulating Bmhsp19.9 and impeding the nuclear localization of the viral proteins P6.9 and VLF-1, leading to the production of defective viral particles. This study offers a comprehensive analysis of the antiviral mechanism in silkworms from a viral perspective, providing a crucial theoretical foundation for future antiviral research and the breeding of resistant silkworm strains., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest to report regarding the present study., (Copyright © 2024. Published by Elsevier B.V.)

In this study, the morphology and ultrastructure of the compound eye of Asi. xanthospilota were examined by using scanning electron microscopy (SEM), transmission electron microscopy (TEM), micro-computed tomography (μCT), and 3D reconstruction. Spectral sensitivity was investigated by electroretinogram (ERG) tests and phototropism experiments. The compound eye of Asi. xanthospilota is of the apposition type, consisting of 611.00 ± 17.53 ommatidia in males and 634.8 0 ± 24.73 ommatidia in females. Each ommatidium is composed of a subplano-convex cornea, an acone consisting of four cone cells, eight retinular cells along with the rhabdom, two primary pigment cells, and about 23 secondary pigment cells. The open type of rhabdom in Asi. xanthospilota consists of six peripheral rhabdomeres contributed by the six peripheral retinular cells (R1~R6) and two distally attached rhabdomeric segments generated solely by R7, while R8 do not contribute to the rhabdom. The orientation of microvilli indicates that Asi. xanthospilota is unlikely to be a polarization-sensitive species. ERG testing showed that both males and females reacted to stimuli from red, yellow, green, blue, and ultraviolet light. Both males and females exhibited strong responses to blue and green light but weak responses to red light. The phototropism experiments showed that both males and females exhibited positive phototaxis to all five lights, with blue light significantly stronger than the others.

The Notch signaling pathway is important in cell cycle regulation and cell proliferation. The transcriptional repressor Suppressor of Hairless [Su(H)] is a molecular switch for downstream target genes of the Notch signaling pathway but the regulatory mechanism of the Su(H) gene in the cell cycle is unclear. We determined the function of the Notch signaling pathway and Bombyx mori Su(H) [BmSu(H)] in the regulation of the silkworm cell cycle. Inhibition of Notch signaling promoted the replication of DNA in silkworm gland cells and expression of the BmSu(H) gene was significantly reduced. Overexpression of the BmSu(H) gene inhibited DNA replication and cell proliferation of silkworm cells, whereas knockout of the BmSu(H) gene promoted DNA replication and cell proliferation. Knockout of the BmSu(H) in silkworms improved the efficiency of silk gland cell endoreplication and increased important economic traits. We demonstrated that BmSu(H) protein can directly bind to the promoters of BmCyclinA, BmCyclinE and BmCDK1 genes, inhibiting or promoting their transcription at the cell and individual level. This study identified molecular targets for genetic improvement of the silkworm and also provided insights into the regulatory mechanism of the cell cycle., Competing Interests: Declaration of competing interest The authors declare no conflict of interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Optical grating devices based on micro/nanostructured functional surfaces are widely employed to precisely manipulate light propagation, which is significant for information technologies, optical data storage, and light sensors. However, the parameters of rigid periodic structures are difficult to tune after manufacturing, which seriously limits their capacity for in situ light manipulation. Here, a novel anti-eavesdropping, anti-damage, and anti-tamper dynamic optical encryption strategy are reported via tunable mechanical composite wrinkle micrograting encryption systems (MCWGES). By mechanically composing multiple in-situ tunable ordered wrinkle gratings, the dynamic keys with large space capacity are generated to obtain encrypted diffraction patterns, which can provide a higher level of security for the encrypted systems. Furthermore, a multiple grating cone diffraction model is proposed to reveal the dynamic optical encryption principle of MCWGES. Optical encryption communication using dynamic keys has the effect of preventing eavesdropping, damage, and tampering. This dynamic encryption method based on optical manipulation of wrinkle grating demonstrates the potential applications of micro/nanostructured functional surfaces in the field of information security., (© 2024 Wiley‐VCH GmbH.)

Bombyx mori nucleopolyhedrovirus (BmNPV) is a pathogen that causes significant losses to the silkworm industry. Numerous antiviral genes and proteins have been identified by studying silkworm resistance to BmNPV. However, the molecular mechanism of silkworm resistance to BmNPV is unclear. We analyzed the differences between the susceptible strain 871 and a near-isogenic resistant strain 871C. The survival of strain 871C was significantly greater than that of 871 after oral and subcutaneous exposure to BmNPV. Strain 871C exhibited a nearly 10,000-fold higher LD50 for BmNPV compared to 871. BmNPV proliferation was significantly inhibited in all tested tissues of strain 871C using HE strain and fluorescence analysis. Strain 871C exhibited cellular resistance to BmNPV rather than peritrophic membrane or serum resistance. Strain 871C suppressed the expression of the viral early gene Bm60. This led to the inhibition of BmNPV DNA replication and late structural gene transcription based on the cascade regulation of baculovirus gene expression. Bm60 could also interact with the viral DNA binding protein and alkaline nuclease, as well as host proteins Methylcrotonoyl-CoA carboxylase subunit alpha, mucin-2-like protein, and 30 K-8. Overexpression of 30 K-8 significantly inhibited BmNPV proliferation. These results increase understanding of the molecular mechanism behind silkworm resistance to BmNPV and suggest targets for the breeding of resistant silkworm strains and the controlling pest of Lepidoptera., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Doublecortin-like kinase 3 (DCLK3), a member of tubulin superfamily, has been proved to be closely associated with the pathogenesis of numerous human tumors. However, the expression pattern and regulatory mechanisms of DCLK3 in gastric cancer (GC) remain unknown., Materials and Methods: DCLK3 expression in GC cells was assessed by RT-qPCR and western blotting. The correlation between DCLK3 levels and the overall survival of GC patients was assessed via TCGA, ACLBI, and Kaplan-Meier plotter databases. Additionally, key proteins (TCF4) involved in the regulation of DCLK3 on GC progression were screened by ACLBI database. Cell proliferation, ferroptotic cell death, and oxidative stress markers were measured by EdU staining, immunofluorescence, ELISA, and western blotting assays., Results: DCLK3 was upregulated in GC, and high DCLK3 expression was significantly associated with poor survival of GC patients. Here, DCLK3 knockdown reduced GC cell proliferation, induced ferroptotic cell death, and exacerbated oxidative stress level. Logistic regression analysis showed that TCF4 was an independent prognostic indicator of GC. Mechanistically, DCLK3 promoted TCF4 expression and subsequently upregulated the expression of TCF4 downstream target genes (c-Myc and Cyclin D1). Furthermore, DCLK3 overexpression enhanced GC cell proliferation, but mitigating ferroptotic cell death and oxidative stress. The regulatory mechanism may involve the upregulation of TCF4, c-Myc, and cyclin D1., Conclusions: Our research suggests that DCLK3 modulates the levels of iron and reactive oxygen and may involve regulation of TCF4 pathway, thereby promoting the GC cell growth, indicating that DCLK3 may use as a prognostic marker and therapeutic target for GC patients., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Acute or chronic wounds are common clinical problems. Collagen, with advantages including rich sources, impeccable biocompatibility, and inherent biodegradability, has been widely used in fundamental research and clinical treatment of wound repair with broad prospects of clinical applications. This article provided a brief overview of the role of collagen in various biological processes related to wound healing and also outlined the sources of collagen. Furthermore, the article summarized the application and recent research advancements of collagen-based wound dressings in the field of wound repair.

The development and utilization of coastal saline-alkali lands hold significant importance in mitigating the shortage of cultivated land resources in China, enhancing the agro-ecological environment in coastal saline and alkaline areas, and ensuring national food security. We set up both pot and field trials (randomized block design) at Xinxiang experimental station of Institute of Crop Science, Chinese Academy of Agricultural Sciences (ICS-CAAS) and Dongying Yellow River Delta Modern Agricultural Research Base in Shandong Province in 2021 and 2022, respectively. The experimental materials, Jiliang 1 and Jiliang 2, underwent seed dressing with GKI composites at concentrations of 2.5 and 5 mL·kg -1 . These composites, which contained the main components of gibberellin, kinetin, and indole butyric acid, were denoted as GKI2.5 and GKI5.0, respectively. The control plots (CK) received water seed dressing. The aim was to assess the regulatory effects of GKI on salt tolerance and grain sorghum yield. Compared to CK, the GKI2.5 and GKI5.0 seed dressing treatments significantly enhanced the growth and development of the two grain sorghum varieties, increased antioxidant enzyme activity and soluble protein content of sorghum leaves, while reducing leaf malondialdehyde content. Moreover, the GKI treatments increased leaf net photosynthetic rate. Under field conditions, yields of Jiliang 1 and Jiliang 2 were enhanced by an average of 17.1% and 19.1%, respectively. In conclusion, GKI seed dressing treatment effectively promoted the growth and development of sorghum under salt stress. It enhanced the antioxidant and osmoregulatory capacities of leaves, reduced the level of membrane lipid peroxidation, and improved net photosynthetic rate of leaves, which together improved the salt tolerance and sorghum yield.

Background: Nintedanib (Ninte) has been approved for the treatment of pulmonary fibrosis, and whether it can ameliorate chronic pancreatitis (CP) is unknown., Aims: This study was conducted to investigate the effect and molecular mechanism of Ninte on pancreatic fibrosis and inflammation in vivo and in vitro., Methods: The caerulein-induced CP model of murine was applied, and Ninte was orally administered. Pathological changes in pancreas were evaluated using hematoxylin & eosin, Sirius Red, Masson's trichrome, and anti-Ki-67 staining. For in vitro studies, the effects of Ninte on cell viability, apoptosis, and migration of pancreatic stellate cells (PSCs) were determined by CCK-8, flow cytometry, and wound healing assays, respectively. The potential molecular mechanisms of the effects of Ninte on PSCs were analyzed by RNA-Seq and verified at the gene expression and protein activity levels by qRT-PCR and Western Blot., Results: Ninte significantly alleviated the weight loss in mice with caerulein-induced CP and simultaneously attenuated the pancreatic damage, as evidenced by reduced acinar atrophy, collagen deposition, infiltration of inflammatory cells, and inhibited cell proliferation/regeneration. Besides, Ninte markedly suppressed the transcription of fibrogenic and proinflammatory genes in pancreatic tissues. Further in vitro studies showed that Ninte significantly inhibited the transcription and protein expression of genes corresponding to fibrogenesis and proliferation in PSCs. The results of RNA-Seq analysis and subsequent verification assays indicated that Ninte inhibited the activation and proliferation of PSCs via the JAK/STAT3 and ERK1/2 pathways., Conclusions: These findings indicate that Ninte may be a potential anti-inflammatory and anti-fibrotic therapeutic agent for CP., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The activity of polysaccharides is usually related to molecular weight. The molecular weight of polysaccharides is critical to their immunological effect in cancer therapy. Herein, the Codonopsis polysaccharides of different molecular weights were isolated using ultrafiltration membranes of 60- and 100-wDa molecular weight cut-off to determine the relationship between molecular weight and antitumor activities. First, three water-soluble polysaccharides CPPS-I (<60 wDa), CPPS-II (60-100 wDa), and CPPS-III (>100 wDa) from Codonopsis were isolated and purified using a combination of macroporous adsorption resin chromatography and ultrafiltration. Their structural characteristics were determined through chemical derivatization, GPC, HPLC, FT-IR, and NMR techniques. In vitro experiments indicated that all Codonopsis polysaccharides exhibited significant antitumor activities, with the tumor inhibition rate in the following order: CPPS-II > CPPS-I > CPPS-III. The treatment of CPPS-II exhibited the highest inhibition rate at a high concentration among all groups, which was almost as efficient as that of the DOX·HCL (10 μg/mL) group at 125 μg/mL concentration. Notably, CPPS-II demonstrated the ability to enhance NO secretion and the antitumor ability of macrophages relative to the other two groups of polysaccharides. Finally, in vivo experiments revealed that CPPS-II increased the M1/M2 ratio in immune system regulation and that the tumor inhibition effect of CPPS-II + DOX was superior to that of DOX monotherapy, implying that CPPS-II + DOX played a synergistic role in regulating the immune system function and the direct tumor-killing ability of DOX. Therefore, CPPS-II is expected to be applied as an effective cancer treatment or adjuvant therapy.

Hydrophobic drug delivery vectors suffer significant challenges in cancer therapy, including efficient encapsulation and tumor targeting ability. In the present study, Rhodiola rosea polysaccharides (RHPs), which have the ability to modulate Tumor-associated macrophages and typical structural characteristics, were employed as an immunoactive vector for drug delivery. Folic acid (FA) and stearic acid (SA) were chemically modified to the backbone of RHPs to obtain the self-assembly and tumor-targeting behavior. Further, the hydrophobic drug, doxorubicin (DOX), was encapsulated in the RHPs derivatives (FA-RHPs-SA) with high efficiency. Additionally, the optimally formed DOX@FA-RHPs-SA had a uniform size distribution of approximately 196 nm and a pH-sensitive release capacity in different acidic conditions. In vitro experiments demonstrated that tumor cells could efficiently uptake DOX@FA-RHPs-SA. Furthermore, the modulatory function of the FA-RHPs-SA on RAW264.7 macrophages was also demonstrated in the transition from M0 to M1 phenotypes, and the M2 differentiated into the M1. Finally, the in vivo antitumor study revealed that the inhibitory effect of DOX@FA-RHPs-SA was superior to the DOX monotherapy treatment, and the new preparation functioned synergistically by inducing tumor cell apoptosis and modulating immune cell function. In conclusion, this study described an RHPs-based hydrophobic delivery vector and achieved an additional helpful antitumor effect by modulating Tumor-associated macrophages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: Research on acute pancreatitis (AP) has been ongoing for a long time. It is necessary to summarize and investigate the history of AP research., Methods: Publications related to AP research were retrieved from PubMed. Medical Subject Headings (MeSH) terms, countries, journals, and publication dates were analyzed. Co-occurrence analysis was conducted to illustrate the holistic trend in AP research. A dynamic bar graph, heat maps, and line charts were created to illustrate change trends of MeSH terms., Results: In total, 28,222 publications with 8558 MeSH terms were retrieved from 1941 to 2020. Among these, 16,575 publications with 7228 MeSH terms were from 2001 to 2020. The top 10 MeSH terms showed a considerable change from 1941 to 1970 but remained stable since the 1970s. Four clusters obtained from the co-occurrence analysis were "experiments on animals," "diagnosis and treatment," "prognosis and expectation," and "protein and enzyme." From 1941 to 2020, 33 MeSH terms with increasing trends (MH-I) and 15 MeSH terms with decreasing trends (MH-D) were selected to create a heat map (every decade). Meanwhile, 16 MH-I and 41 MH-D were selected to create the heat map from 2001 to 2020 (every 2 years)., Conclusion: Over the past 80 years, the pathogenesis, treatment, risk management, and experimental model were the main research highlights. Optimal supportive management, minimally invasive treatment, and prediction of prognosis are subjects of interest for clinical practitioners; signal transduction to identify a target for precise treatment is the focus of experimental research in AP., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Apoptosis, as an important part of the immune response, is one of the core events in the host-virus interaction. Studies have shown that long non-coding RNAs (lncRNAs) play important roles in the process of cell apoptosis and pathophysiology. To investigate the apoptosis-related lncRNAs involved in Bombyx mori nucleopolyhedrovirus (BmNPV) infecting silkworms, transcriptome sequencing was conducted based on silkworm cells infected with BmNPV before and after B. mori inhibitor of apoptosis (Bmiap) gene knockout. A total of 23 differentially expressed lncRNAs were identified as being associated with the mitochondrial apoptosis pathway. Moreover, we demonstrated that B. mori LINC5438 has the function of inhibiting apoptosis in silkworm cells. Overexpression of LINC5438 promoted the proliferation of BmNPV, while interference with LINC5438 inhibited its proliferation, indicating that LINC5438 plays an important role in BmNPV infection. Our results also showed that LINC5438 can regulate the expression of Bmiap, BmDronc, BmICE, and its predicted target gene BmAIF, suggesting that LINC5438 may function through the mitochondrial pathway. These findings provide important insights into the mechanisms of virus-host interaction and the applications of baculoviruses as biological insecticides., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest exists., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abstract: Metastases of prostate carcinoma in the skeleton are usually multiple. Solitary metastasis in appendicular skeleton is extremely rare. We present bone scan findings of solitary scapular metastasis from prostate adenocarcinoma as the initial presentation of his malignancy in a 62-year-old man. The 99mTc-MDP SPECT/CT demonstrated intense activity in the coracoid process of left scapula, whereas the tracer uptakes in other bones were not typical of metastases. The subsequent pathological results of the punctured left scapula confirmed as metastasis from prostate adenocarcinoma., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflicts of interest. This study was supported by the Nature Science Foundation of Hebei Province (H2020206422)., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Chronic refractory wounds and scars caused by abnormal wound repair seriously damage the health of patients and affect their quality of life. At present, there is a lack of simple but effective and economical treatment methods. Adipose-derived stem cells (ASCs), as a kind of mesenchymal stem cells with multi-directional differentiation potential, have been confirmed by several in vivo and in vitro studies to promote wound healing by promoting epithelialization, angiogenesis, immunoregulation, antioxidant properties, and other mechanisms. ASCs and their derivatives have been used in the treatment of refractory wounds caused by burns, diabetic, and radiation injuries with good results achieved. Their potential to become new materials for wound repair has also been confirmed. This paper reviewed the mechanism and clinical application of ASCs in promoting wound repair, and looked into its research direction and prospects.

Background: Postprocedural delayed bleeding (PDB) remains the most common major complication of colorectal polypectomy. Incomplete clip closure of mucosal defect and unclosed injured blood vessels in gaps between clips may be the risk factors for PDB., Objectives: To observe whether completely no-gap closure of mucosal defect after polypectomy can reduce PDB occurrence., Design: Single-center, retrospective case-control study., Methods: In this study based on historical comparisons of patients in 2 time periods, only the patients with polyps sized between 6 and 15 mm were included. A new clip-assisted endoloop ligation (CAEL, treatment group) method was used between January 2019 and December 2020, and a traditional simple clip closure (SCC, control) was used Between January 2017 and December 2018 to prevent PDB after polypectomy. The rate of PDB of two groups and risk factors for PDB were evaluated., Results: Totally 4560 patients were included in the study; 2418 patients belong to CAEL group, and 2142 patients belong to SCC group. The overall rate of PDB was significantly lower in CAEL group compared to SCC group (0.6% versus 1.5%, p  < 0.00). On multivariate logistic analysis, CAEL was a significant independent preventive factor for PDB (odds ratio (OR), 0.092; 95% confidence interval (CI), 0.029-0.3335; p  = 0.000). Polyps located at rectum (colon versus rectum) represented a significant independent risk factor for PDB (OR, 11.888; 95% CI, 3.343-42.269; p  = 0.001)., Conclusion: Completely no-gap closure of mucosal defect after polypectomy further reduced the rate of PDB for polyps sized between 6 and 15 mm. CAEL may be a significant independent preventive factor for PDB. Polyps located at the rectum may be a significant independent risk factor for PDB., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2022.)

Objectives: Our goal was to investigate whether laboratory signatures on admission could be used to identify risk stratification and different tolerance to hypothermic circulatory arrest in acute type A aortic dissection surgery., Methods: Patients from 10 Chinese hospitals participating in the Additive Anti-inflammatory Action for Aortopathy & Arteriopathy (5A) study were randomly divided into derivation and validation cohorts at a ratio of 7:3 to develop and validate a simple risk score model using preoperative variables associated with in-hospital mortality using multivariable logistic regression. The performance of the model was assessed using the area under the receiver operating characteristic curve. Subgroup analyses were performed to investigate whether the laboratory signature-based risk stratification could differentiate the tolerance to hypothermic circulatory arrest., Results: There were 1443 patients and 954 patients in the derivation and validation cohorts, respectively. Multivariable analysis showed the associations of older age, larger body mass index, lower platelet-neutrophile ratio, higher lymphocyte-monocyte ratio, higher D-dimer, lower fibrinogen and lower estimated glomerular filtration rate with in-hospital death, incorporated to develop a simple risk model (5A laboratory risk score), with an area under the receiver operating characteristic of 0.736 (95% confidence interval 0.700-0.771) and 0.715 (95% CI 0.681-0.750) in the derivation and validation cohorts, respectively. Patients at low risk were more tolerant to hypothermic circulatory arrest than those at middle to high risk in terms of in-hospital mortality [odds ratio 1.814 (0.222-14.846); odds ratio 1.824 (1.137-2.926) (P = 0.996)]., Conclusions: The 5A laboratory-based risk score model reflecting inflammatory, immune, coagulation and metabolic pathways provided adequate discrimination performances in in-hospital mortality prediction, which contributed to differentiating the tolerance to hypothermic circulatory arrest in acute type A aortic dissection surgery.Clinical Trials. gov number NCT04918108., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: Immune dysregulation plays a key role in major depressive disorder (MDD). However, little is known about the complicated involvement of various interleukins in MDD. This study was performed to investigate the correlation between plasma interleukin-8 (IL-8) levels and treatment outcome of paroxetine (a selective serotonin reuptake inhibitor) in patients with MDD., Methods: A total of 115 hospitalized patients (36 males and 79 females), aged from 18 to 72 years, were enrolled. Plasma levels of IL-8 were measured before treatment initiation (baseline) and at 8 weeks after oral paroxetine treatment. Efficacy of paroxetine was evaluated by use of the Hamilton Depression Rating Scale (HAMD-17). Baseline IL-8 levels were compared between responders and non-responders to paroxetine treatment., Results: Plasma IL-8 levels decreased significantly after an 8-week antidepressant treatment in responders, in association with a dramatic decrease in HAMD-17 scores. In non-responders, plasma IL-8 levels did not change significantly at 8 weeks after antidepressant treatment. Baseline plasma IL-8 levels were found to be significantly lower in responders than in non-responders, showing a correlation between IL-8 and antidepressant response to paroxetine., Conclusions: These results indicate that plasma IL-8 levels were related to treatment outcome of paroxetine, and therefore suggest that IL-8 could be a promising predicator of treatment response in individual patients with MDD., (© 2022 John Wiley & Sons Ltd.)

Acute pancreatitis (AP) is a common digestive disease encountered in Emergency Departments that carries a heavy socioeconomic burden. This study was conducted to determine the global status of AP research. Articles related to AP published in 1999 to 2018 were retrieved from the Web of Science (WOS) database and the 20 highest-output countries or regions were determined based on the total number of publications. Correlation analysis of AP research output and the gross domestic product (GDP) of each country or region was conducted. The quantity and quality of research of these 20 highest-output countries were compared to the total output, outputs per capita, and average impact factor (IF). All annual data were analyzed using time-trend analysis. A keyword co-occurrence analysis was conducted to determine the highlights in AP research. In total, 17,698 publications were retrieved, and 16,461 papers (93.0%) of them were from the 20 highest-output countries. A significantly positive correlation was identified between AP research output and the GDP (R = 0.973, P < .001). The 5 highest-output countries were the USA (24.9%), China (12.3%), Germany (7.5%), Japan (6.7%), and the UK (6.1%). Finland ranked 1st in the number of publication per capita, the USA had the highest accumulated IF (25,432.758) and total citations (104,592), Switzerland had the highest average IF (6.723), and Netherland had the highest average citations (51.90). Genetic research and AP-related hyperglycemia were research highlights. Analysis of the global output of research of AP research showed signs of growth. Research output was positively correlated with GDP. For the most productive countries, research quality was stable. Although developing countries lagged behind in output per capita and quality, great progress has been made in the past 2 decades., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The immediate early protein 1 (IE1) acts as a transcriptional activator and is essential for viral gene transcription and viral DNA replication. However, the key regulatory domains of IE1 remain poorly understood. Here, we analyzed the sequence characteristics of Bombyx mori nucleopolyhedrovirus (BmNPV) IE1 and identified the key functional domains of BmNPV IE1 by stepwise truncation. Our results showed that BmNPV IE1 was highly similar to Autographa californica nucleopolyhedrovirus (AcMNPV) IE1, but was less conserved with IE1 of other baculoviruses, the C-terminus of IE1 was more conserved than the N-terminus, and BmNPV IE1 was also necessary for BmNPV proliferation. Moreover, we found that IE1 158-208 was a major nuclear localization element, and IE1 1-157 and IE1 539-559 were minor nuclear localization elements, but the combination of these two minor elements was equally sufficient to fully mediate the nuclear entry of IE1. Meanwhile, IE1 1-258 , IE1 560-584 , and the association of amino acids 258 and 259 were indispensable for the transactivation activity of BmNPV IE1. These results systematically resolve the functional domains of BmNPV IE1, which contribute to the understanding of the mechanism of baculovirus infection and provide a possibility to synthesize a small molecule IE1-truncated mutant as an agonist or antagonist.

Objective: The pathogenesis of chronic pancreatitis (CP) is not completely clear. With further studies, smoking is toxic to the pancreas. This study classified smoking-related CP as a new etiology of CP and defined the cutoff of smoking., Design: Patients with CP admitted from January 2000 to December 2013 were included in the study. The characteristics were compared between smoking patients, drinking patients, and a group of patients who never smoke or drink (control group). The cumulative rates of steatorrhea, diabetes mellitus (DM), pancreatic pseudocyst (PPC), pancreatic stone, and biliary stricture after the onset of CP were calculated, respectively., Results: A total of 1,324 patients were included. Among them, 55 were smoking patients, 80 were drinking patients, and 1,189 were controls. The characteristics of smokers are different from the other two groups, especially in age at the onset and diagnosis of CP, initial manifestation, and type of pain. The development of DM ( P = 0.011) and PPC ( P = 0.033) was significantly more common and earlier in the smokers than in the other two groups. Steatorrhea also developed significantly more in the smokers than in the controls ( P = 0.029). Smokers tend to delay the formation of pancreatic stones and steatorrhea., Conclusion: The clinical characteristics of smoking-related CP is different from CP of other etiologies. A new type of CP, smoking-related CP, was put forward. Smoking-related CP should be separated from idiopathic CP and defined as a new independent subtype of CP different from alcoholic CP or idiopathic CP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hao, Liu, Dong, Yi, Wang, Xin, Guo, He, Bi, Ji, Wang, Du, Lin, Zhang, Zeng, Zou, Chen, Pan, Liao, Xu, Li and Hu.)

The E2F family of transcription factors is crucial for cell cycle progression and cell fate decisions. Although E2Fs have been widely studied in mammals, there have been few studies performed in insects. Here, we determined the function of E2F4 in the silkworm, Bombyx mori. We demonstrate that E2F proteins are highly conserved among species from lower animals to higher mammals. Overexpression of the BmE2F4 gene led to cell cycle arrest in the G1 phase, whereas interfering with the BmE2F4 mRNA led to accumulation of cells in the S phase. These results indicate that BmE2F4 is important in cell cycle regulation. We also demonstrate that the BmE2F4 gene is involved in DNA replication of BmN-SWU1 cells and DNA synthesis in the silk gland. Furthermore, we identified a protein called Bm14-3-3ζ that can interact with BmE2F4 and allow it to localize in the nucleus. Overexpression of the Bm14-3-3ζ gene led to cell cycle arrest in the G1 phase, while knocking down the gene increased the proportion of cells in S phase. These findings provide important insights into the function of E2F transcription factors and increase our understanding of their involvement in cell cycle regulation., (© 2021 Institute of Zoology, Chinese Academy of Sciences.)

Renal fibrosis (RF) is a chronic and fatal disease related to the gradual deterioration of kidney function. MicroRNAs (miRNAs) play a key role in cellular functions and several of them related to the pathogenesis of RF have been identified, although the underlying mechanisms are unclear. In order to explore the miRNAs involved in RF progression, we established a model in rats by the unilateral ureteral ligation method. The animals were randomly divided into the control group, and the 2 week, 4 week and 6 week model groups. The indices of renal function were measured using routine biochemical assays. The differentially expressed miRNAs (DE-miRNAs) between the sham-operated and modelled rats were screened, and their putative target genes were identified using the miRanda software and functionally annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The expression of transforming growth factor β1 (TGF-β1), Smad3 and Smad7 was confirmed by RT-PCR. Compared to the sham-operated group, the model groups showed a decrease in SOD activity, along with the increased renal coefficient, and higher MDA, HYP, Scr, BUN and ALB levels. In addition, TGF-β1, Smad3 and Smad7 were also upregulated in the RF groups. We identified 274 known and 11 novel DE-miRNAs in the 2 week, 114 known and 6 novel DE-miRNAs in the 4 week, and 41 known and 1 novel DE-miRNAs in the 6 week model groups. The putative target genes of these DE-miRNAs were enriched in metabolic processes, apoptosis, pyrimidine metabolism, and TNF and VEGF signalling pathways. Based on our findings, we surmise that miR-146a-3p, miR-148a-3p, miR-130a-5p, miR-362-3p and miR-122-5p are likely to be involved in the occurrence and development of RF, and miR-122-5p may play an inhibitory role. The underlying mechanisms need further investigation.

Objectives: Steatorrhea, a sign of severe pancreatic exocrine insufficiency (PEI), is related to consequences caused by pancreatitis. This study aimed to identify predictors and to construct a nomogram for steatorrhea in idiopathic chronic pancreatitis (ICP)., Methods: ICP patients admitted to our hospital from January 2000 to December 2013 were enrolled in this retrospective-prospective cohort study and randomly assigned to the training and validation cohorts. The cumulative rate of steatorrhea was calculated. A Cox proportional hazard regression model was used to identify predictors for steatorrhea and construct the nomogram. Internal and external validation of the nomogram was then performed., Results: There were 1633 ICP patients enrolled, with a median follow-up duration of 9.8 years and 20.8% (339/1633) of patients developed steatorrhea following onset of ICP. Steatorrhea was observed in 93, 115, and 133 patients at 1, 3, and 5 years following diagnosis of CP, with a cumulative rate of 6.5% (95% confidence interval [CI] 5.1%-7.9%), 8.0% (95% CI 6.2%-9.8%), and 9.3% (95% CI 6.6%-12.0%), respectively. Male sex (hazard ratio [HR] 2.479, P < 0.001), diabetes mellitus at/before diagnosis of ICP (HR 2.274, P = 0.003), and aged less than 18 years at onset of ICP (HR 0.095, P < 0.001) were identified risk factors for steatorrhea. Initial manifestations were associated with development of steatorrhea. The nomogram was proven to have good concordance indexes., Conclusions: We identified predictors and developed a nomogram for predicting steatorrhea in ICP. It was recommended that high-risk populations be followed up closely, which might contribute to the early diagnosis and treatment of PEI., (© 2022 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Needle knife papillotomy (NKP) and fistulotomy (NKF) are the two most commonly used rescue techniques for patients with difficult biliary cannulation (DBC). Anatomy of the major duodenal papillae (MDP) influences the optimal precut technique for biliary access. However, comparative studies of the success and safety of NKP and NKF based on the anatomy of MDP have been scarce., Methods: Patients with intact MDPs for therapeutic endoscopic retrograde cholangio-pancreatography (ERCP) in our center were enrolled. Early needle knife precuts were uniformly applied to patients with DBC. Difficult MDPs were classified into one of five types based on their endoscopic anatomy. Each type of MDP was allocated to NKP or NKF treatment. Patients with types 1 and 2 papillae always received NKF, 3 and 4 received NKP, and 5 could receive either. The safety and efficacy were analyzed between NKP and NKF, and among different types of MDPs., Results: A total of 188 out of 1674 patients undergoing ERCP satisfied the criteria for early precutting: 75 patients were assigned to the NKP group and 113 to the NKF group. The total initial success rate of biliary cannulation (ISRBC) of the precut techniques (both NKP and NKF) for patients with DBC was 91.5%. The ISRBC of patients of the NKP group was similar to that of the NKF group (90.7% vs 92.0%, P > 0.05). The ISRBC of the patients in the swollen MDP subgroup (96.1%) was higher than that of patients in the distorted MDP subgroup (81.8%, P = 0.030). The total and specific complications of the patients of the NKP group were similar to those of the NKF group (P > 0.05)., Conclusions: NKP and NKF, as selected on the basis of MDP anatomy, are equally safe and highly efficient for patients with DBC to allow biliary cannulation. Patients with swollen MDPs had a higher ISRBC than patients with distorted MDPs. Selecting a precut method based on MDP anatomy is an effective and safe strategy for patients with DBC., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Larvae of some leaf beetles carry masses of feces covering parts or all of the body, which is called a "fecal shield". In general, the shield is thought to be a defense structure against natural enemies. However, some studies have suggested that defense effectiveness varies depending on the natural enemy. In this study, we used a fecal retention leaf beetle Ophrida xanthospilota (Coleoptera: Chrysomelidae), and 2 local generalist predators (an ant, Camponotus japonicus (Hymenoptera: Formicidae) and a stinkbug, Arma custos [Hemiptera: Pentatomidae]) as a system to test the hypothesis that the fecal shield of O. xanthospilota plays different roles in predation behavior of different predators and can provide multiple chemical communication signals in predator-prey interactions. Prey bioassays showed that the fecal shield of O. xanthospilota larvae repelled the ant C. japonicus while attracting the stinkbug A. custos. The results also strongly demonstrated that hexane extracts of the fecal shield significantly repelled C. japonicus , while dichloromethane (DCM) extracts did not inhibit ant predation. Interestingly, DCM extracts attracted A. custos , but hexane extracts did not. Therefore, we suggest that the fecal shield is a double-edged sword for the larvae of O. xanthospilota . Our results also indicated that the risk-benefit tradeoff of an insect should be estimated at a community level involving multiple enemies (predators and parasites) and herbivores, rather than in a single prey-predator pair., Competing Interests: The authors declare that they have no conflicts of interest related to this work., (© The Author(s) 2022. Published by Oxford University Press on behalf of Editorial Office, Current Zoology.)

Objective: To evaluate of the clinical effects of mobile-bearing(MB) and fixed-bearing(FB) unicompartmental knee arthroplasty(UKA) in the treatment of knee osteoarthritis by Meta-analysis., Methods: The literature on FB UKA and MB UKA in the treatment of knee osteoarthritis in PubMed, CNKI, Wanfang, Cochrane and EMBASE database were searched by computer from January 2000 to April 2020. According to the inclusion and exclusion criteria, two authors were selected independently and the selected literature was evaluated for quality.After literature data were extracted, Review Manager 5.3 software was used to analyze knee function score, postoperative activity, revision rate, polyethylene wear rate, pad dislocation, aseptic loosening, postoperative pain, knee arthritis progression, mechanical shaft alignment of lower limbs, and imaging clarity line respectively., Results: A total of 13 literatures were included in this meta-analysis, including 2 randomized controlled studies and 11 cohort studies. A total of 1 871 patients were included, including 913 in FB UKA group and 958 in MB UKA group. Meta analysis results showed that:postoperative knee joint function score[ MD =-0.84, 95% CI (-1.46, -0.21), P =0.008] and postoperative knee joint range of motion [ MD =-1.51, 95% CI (-2.84, -0.18), P =0.03] in FB UKA group were better than those in MB UKA group. Compared with FB UKA group, MB UKA group had a higher lower limb mechanical axis alignment rate[ OR =2.08, 95% CI (1.27, 3.39), P =0.003], and the wear rate of polyethylene [ OR =0.11, 95% CI (0.01, 0.91), P =0.04] was lower. There were no differences between two groups in the renovation rate [ OR =1.16, 95% CI (0.75, 1.80), P =0.50), liner dislocation rate[ OR =3.78, 95% CI (0.93, 15.29), P =0.06], aseptic loosening [ OR =2.11, 95% CI (0.81, 5.51), P =0.13], postoperative pain[ OR =1.13, 95% CI (0.37, 3.43), P =0.83], osteoarthritis progression[ OR =1.28, 95% CI (0.67, 2.47), P =0.46)and imaging radiolucent line[ OR =1.62, 95% CI (0.09, 30.22), P =0.75]., Conclusion: FB UKA has a higher postoperative functional score and range of motion.MB UKA has more advantages in the correction of lower limb mechanical axis, and the wear rate of polyethylene is also lower. There was no significant difference between the two groups in revision rate, dislocation of the liner, aseptic loosening, postoperative pain, progression of osteoarthritis, and postoperative translucency.

Understanding virus-host interaction is very important for delineating the mechanism involved in viral replication and host resistance. Baculovirus, an insect virus, can cause S or G2/M phase arrest in insect cells. However, the roles and mechanism of Baculovirus-mediated S or G2/M phase arrest are not fully understood. Our results, obtained using flow cytometry (FCM), tubulin-labeling, BrdU-labeling, and CellTiter 96 ® AQueous One Solution Cell Proliferation Assay (MTS), showed that Bombyx mori nucleopolyhedrovirus (BmNPV) induced G2/M phase arrest and inhibited cellular DNA replication as well as cell proliferation in BmN-SWU1 cells. We found that BmNPV induced G2/M arrest to support its replication and proliferation by reducing the expression of BmCDK1 and BmCyclin B . Co-immunoprecipitation assays confirmed that BmNPV IAP1 interacted with BmCDK1. BmNPV iap1 was involved in the process of BmNPV-induced G2/M arrest by reducing the content of BmCDK1. Taken together, our results improve the understanding of the virus-host interaction network, and provide a potential target gene that connects apoptosis and the cell cycle.

An efficient and environmentally friendly ultrasound-assisted (UAE) natural deep eutectic solvent (NADES) extraction method was applied for the extraction of five bioactive compounds (liquiritin, isoliquiritin, liquiritigenin, glycyrrhizic acid and isoliquiritigenin) from compound liquorice tablets (CPLTs), and the antioxidant activities of these compounds were evaluated. In this study, eighteen different NADES systems based on either two or three components were tested and a 1,4-butanediol-levulinic acid system (1 : 3 molar ratio) was selected as a topgallant solvent for maximizing analyte extraction yields. Various extraction parameters, such as water content, liquid/solid ratio, extraction time and temperature, were systematically optimized by single-factor and response surface methodology (RSM) experiments. The results indicated that the optimum extraction conditions for the analytes featured a water content of 17%, a liquid/solid ratio of 42 mL g -1 and an extraction time of 30 min. The extracted amounts of liquiritin, isoliquiritin, liquiritigenin, glycyrrhizic acid and isoliquiritigenin reached 5.60, 3.17, 1.27, 74.62 and 1.34 mg g -1 , respectively, under optimized conditions, which were much higher than those extracted using conventional organic solvents. In addition, antioxidant tests revealed that the NADES extracts showed higher DPPH and hydroxyl radical-scavenging capacity than the conventional solvent extracts used for comparison. This study provides a suitable approach for efficiently extracting the bioactive compounds of CPLTs. Meanwhile, NADESs can be extended to other natural products as green extraction media., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Cell division cycle protein 37 (Cdc37) is a molecular chaperone that actively participates in many intracellular physiological and biochemical processes as well as pathogen infection. However, the function of Cdc37 in silkworm cells under Bombyx mori nucleopolyhedrovirus (BmNPV) infection is unknown. We cloned and identified BmCdc37, a Cdc37 gene from B. mori, which is highly conserved among other species. After BmNPV infection, the expression level of the BmCdc37 gene was up-regulated and showed an expression pattern similar to the BmHsp90 gene, which relies on Cdc37 to stabilize and activate specific protein kinases. The immunofluorescence, bimolecular fluorescence complementation (BiFC), and co-immunoprecipitation (Co-IP) assays all indicated that BmCdc37 interacts with BmHsp90 in silkworm cells. Both BmCdc37 and BmHsp90 promote the reproduction of BmNPV. Co-expression of BmCdc37 and BmHsp90 was better at promoting virus proliferation than overexpression alone. These findings all indicate that BmCdc37 plays an active role in the proliferation of BmNPV., (Copyright © 2021. Published by Elsevier Inc.)

In this study, we studied the solubility and permeability of matrine, oxymatrine, sophoridine, and oxysophocarpine, four alkaloids in the Mongolian herbal medicine Sophorae Flavescentis Radix, and evaluated the absorption mechanism with the Caco-2 cell model, so as to provide a basis for the new drug development and efficacy evaluation of Sophorae Flavescentis Radix. The results showed that all the four alkaloids had high solubility and high permeability and can be well absorbed, belonging to the class-I drugs of Biopharmaceutical Classification System(BCS). The absorption(AP→BL) and excretion(BL→AP) of matrine and oxymatrine were not affected by the concentration while the absorption depended on P-gp protein. The absorption(AP→BL) and excretion(BL→AP) of sophoridine and oxysophocarpine were positively related to the concentration and time, and the absorption process was independent from P-gp protein. The results provide scientific reference and an experimental basis for the development of Mongolian medical prescriptions containing Sophorae Flavescentis Radix.

The trachea of insects is a tubular epithelia tissue that transports oxygen and other gases. It serves as a useful model for the studying of the cellular and molecular events involved in epithelial tube formation. Almost all of the extracellular matrix can be degraded by Matrix metalloproteinases (MMPs), which is closely related to the processes of development and regeneration. The regulation of trachea by MMPs is roughly known in previous studies, but the detailed regulation mechanism and involved gene function are not fully explored. In this article, we found MMP1 expressed highly during tracheal remodeling, and knocked out it makes the tracheal branch number reduced in Bombyx mori . In trachea of transgenic BmMMP1-KO silkworm, the space expanding of taenidium and epidermal cells and the structure of apical membrane were abnormal. To explore the underlying mechanism, we detected that DE-cadherin and Integrin β1 were accumulated in trachea of transgenic BmMMP1-KO silkworm by immunohistochemistry. Moreover, 5-Bromo-2'-Deoxyuridine (BrdU) labeling showed that knockout of BmMMP1 in silkworm inhibited tracheal cell proliferation, and BmMMP1 also regulated the proliferation and migration of BmNS cells. All of the results demonstrated that BmMMP1 regulates the development of the tracheal tissue by expanding the space of tracheal cuticles and increases the number of tracheal branches by degrading DE-cadherin and Integrin β1.

Energy metabolism is important for the proliferation of microsporidia in infected host cells, but there is limited information on the host response. The energy metabolism response of silkworm (Bombyx mori) to microsporidia may help manage Nosema bombycis infections. We analyzed differentially expressed genes in the B.mori midgut transcriptome at two significant time points of microsporidia infection. A total of 1448 genes were up-regulated, while 315 genes were down-regulated. A high proportion of genes were involved in the phosphatidylinositol signaling system, protein processing in the endoplasmic reticulum, and glycerolipid metabolism at 48 h post infection (h p.i.), and a large number of genes were involved in the TCA cycle and protein processing at 120 h p.i. These results showed that the early stages of microsporidia infection affected the basic metabolism and biosynthesis processes of the silkworm. Knockout of Bm&#95;nscaf2860&#95;46 (Bombyx mori isocitrate dehydrogenase, BmIDH) and Bm&#95;nscaf3027&#95;062 (Bombyx mori hexokinase, BmHXK) reduced the production of ATP and inhibited microsporidia proliferation. Host fatty acid degradation, glycerol metabolism, glycolysis pathway, and TCA cycle response to microsporidia infection were also analyzed, and their importance to microsporidia proliferation was verified. These results increase our understanding of the molecular mechanisms involved in N. bombycis infection and provide new insights for research on microsporidia control. IMPORTANCE: Nosema bombycis can be vertically transmitted in silkworm eggs. The traditional prevention and control strategies for microsporidia are difficult and time-consuming, and this is a problem in silkworm culture. Research has mainly focused on host gene functions related to microsporidia infection and host immune responses after microsporidia infection. Little is known about the metabolic changes occurring in the host after infection. Understanding the metabolic changes in the silkworm host could aid in the recognition of host genes important for microsporidia infection and growth. We analyzed host metabolic changes and the main participating pathways at two time points after microsporidia infection and screened the microsporidia-dependent host energy metabolism genes BmIDH and BmHXK. The results revealed genes that are important for the proliferation of Nosema bombycis. These results illustrate how microsporidia hijack the host genome for their growth and reproduction., (Copyright © 2021. Published by Elsevier Inc.)

In the present study, the magnetic field induced self-assembly processes of magnetic microparticles in an aqueous liquid (the pure magnetic fluid) and nonmagnetic microparticles in ferrofluid (the inverse magnetic fluid) are experimentally investigated. The microparticles are formed into chain-like microstructures in both the pure magnetic fluid and the inverse magnetic fluid by applying the external magnetic field. The fluorescence parameters of these self-assembled chain-like microstructures are measured and compared to those without the effect of magnetic field. It is found that the fluorescence in the pure magnetic fluid is weakened, because the scattering and illuminating areas are reduced in the microstructures. On the contrary, the fluorescence in the inverse magnetic fluid is enhanced, because more fluorescent nonmagnetic microparticles are enriched and become detectable under the effect of the magnetic dipole force and the magnetic levitational force, and their unnecessary scattering can be absorbed by the surrounding ferrofluid. The average enhancement of the fluorescence area ratio in the inverse magnetic fluid with 3  μ m nonmagnetic microparticles reaches 112.92%. The present work shows that the inverse magnetic fluid has advantages such as low cost, no scattering effect, stable fluorescence intensity, and relatively low magnetic resistance. In the end, a prototype design for the novel detection of coronavirus disease 2019 based on the magnetic field induced self-assembly in the inverse magnetic fluid is proposed, which could support the epidemic prevention and control., (© 2021 Author(s).)

Objective: To perform a bibliometric analysis of research on articular cartilage repair published in Chinese and English over the past decade. Fundamental and clinical research topics of high interest were further comparatively analyzed., Methods: Relevant studies published from 1 January 2009 to 31 December 2018 (10 years) were retrieved from the Wanfang database (Chinese articles) and six databases, including MEDLINE, WOS, INSPEC, SCIELO, KJD, and RSCI on the website "Web of Science" (English articles), using key words: "articular cartilage" AND "injury" AND "repair". The articles were categorized according to research focuses for a comparative analysis between those published in Chinese vs English, and further grouped according to publication date (before and after 2014). A comparative analysis was performed on research focus to characterize the variation in research trends between two 5-year time spans. Moreover, articles were classified as basic and clinical research studies., Results: Overall, 5762 articles were retrieved, including 2748 in domestic Chinese journals and 3014 in international English journals. A total of 4937 articles focused on the top 10 research topics, with the top 3 being stem cells (32.1%), tissue-engineered scaffold (22.8%), and molecular mechanisms (16.4%). Differences between the numbers of Chinese and English papers were observed for 3 topics: chondrocyte implantation (104 vs 316), osteochondral allograft (27 vs 86), and microfracture (127 vs 293). The following topics gained more research interest in the second 5-year time span compared with the first: microfracture, osteochondral allograft, osteochondral autograft, stem cells, and tissue-engineered scaffold. Articles with a focus on three-dimensional-printing technology have shown the fastest increase in publication numbers. Among 5613 research articles, basic research studies accounted for the majority (4429), with clinical studies described in only 1184 articles. The top 7 research topics of clinical studies were: chondrocyte implantation (28.7%), stem cells (21.9%), microfracture (19.2%), tissue scaffold (10.6%), osteochondral autograft (10.5%), osteochondral allograft (6.3%), and periosteal transplantation (2.8%)., Conclusion: Studies focused on stem cells and tissue-engineered scaffolds led the field of damaged articular cartilage repair. International researchers studied allograft-related implantation approaches more often than Chinese researchers. Traditional surgical techniques, such as microfracture and osteochondral transplantation, gained high research interest over the past decade., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

This work presents a facile strategy to develop a flexible polyaniline (PANI)-based supercapacitor (SC) with both high energy density and good capacitance retention. An electrode with a symmetrical sandwich-structured configuration (PANI/flexible porous support/PANI) is used as both working and counter electrodes for this supercapacitor. For a conventional electrode with PANI depositing on single side of the support (PANI/flexible support), the flexible support bends severely during the PANI electrodeposition process, which results in poor PANI deposition. On the contrary, for the symmetrical sandwich-structured electrode, due to the stress-compensation effect induced by this configuration, the support bending is significantly suppressed and thus PANI films with a good uniformity are realized. Moreover, the stress-compensation effect involved in the symmetrical sandwichstructured electrode can also effectively balance the stress caused by PANI expansion/shrinkage during its electrochemical charge/discharge operation, thus improving the mechanical stability. The symmetrical sandwich-structured electrode has larger PANI mass loading, better PANI morphologies and stronger mechanical stability than those of the conventional electrode. Consequently, the SC constructed by the symmetrical sandwich-structured electrode displays better electrochemical performance in terms of its larger specific areal capacitance (369.2 mF·cm -2 at a current density of 0.25 mA·cm -2 ), higher energy density (0.031 mWh·cm -2 at a power density of 1.21 mW·cm -2 ) and better cycling retention (93.2% of the retained capacity over 6000 cycles) than the SC constructed by the conventional electrode.

To clarify the effects of combined applications of chlorocholine chloride (CCC) and nitrogen fertilizer (CN) on nitrogen metabolism and nitrogen use efficiency of summer maize, we conducted a field experiment in Xinxiang experimental station of Chinese Academy of Agricultural Sciences in 2018 and 2019, with four nitrogen application rates (0, 62.5, 125 and 187.5 kg·hm -2 ), and two maize varieties of Jingnongke 728 (JNK728) and Zhongdan 909 (ZD909). The results showed that across the two years CN-CCC increased maize yield by 7.7% and 5.0% under the nitrogen application rates of 62.5 kg·hm -2 and 125 kg·hm -2 , respectively. CN-CCC increased the contents of nitrate reductase, glutamine synthetase, glutamate synthetase and soluble protein, and finally promoted nitrogen metabolism. Under the low and middle nitrogen application conditions (62.5 kg·hm -2 and 125 kg·hm -2 ), plant nitrogen content of JNK728 and ZD909 increased by 17.6% and 30.3%, grain nitrogen content increased by 10.3% and 17.4%, nitrogen partial productivity, agronomic efficiency of applied nitrogen, recovery efficiency of applied nitrogen, nitrogen use efficiency increased by 10.0%, 15.7%, 23.3%, 24.8% and 5.7%, 15.0%, 49.9%, 71.7%, respectively. In conclusion, appropriate basic application of CN-CCC could enhance nitrogen metabolism, increase nitrogen use efficiency and grain yield of summer maize. Our results showed that CCC combined basic nitrogen application of 125 kg·hm -2 had the best effect.