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Staphylococcus pseudintermedius ( S. pseudintermedius ) is the main pathogen causing pyoderma of canines. With the emergence of drug-resistant bacteria, traditional antibiotic treatments are limited. As a potential antibacterial agent, NZ2114 was effective against S. pseudintermedius , including drug-resistant strains. Its bactericidal efficacy was superior to mupiroxacin, ofloxacin and lincomycin. To facilitate the transcutaneous delivery of NZ2114 for the treatment of superficial pyoderma, chemical permeation enhancers were added since water-soluble NZ2114 does not easily penetrate the skin lipid layer. Two different NZ2114 sprays were prepared by combining 1% Azone + 10% propylene glycol (PG) or 5% N-methylpyrrolidone (NMP) + 10% PG with NZ2114 after screening. The cumulative permeability of NZ2114 sprays were 244.149 and 405.245 μg/cm 2 at 24 h with an in vitro percutaneous assay of mice skin, which showed a 244% and 405% increase in skin permeability than NZ2114, respectively. In addition, the efficacy of NZ2114 sprays in reducing skin bacteria colonisation was demonstrated in a mouse model of superficial pyoderma (24 mice, 3 mice/group) induced by S. pseudintermedius , and the 5% NMP + 10% PG + NZ2114 group had the best therapeutic effect compared to the other groups. This preparation did not cause any skin irritation, laying the foundation for the development of an effective and non-toxic topical product.

A simple and efficient method for the synthesis of spiropyridazine-benzosultams has been developed by means of [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes. This approach displays advantages such as mild reaction conditions, wide substrate range tolerance, simple operation, compatibility with gram-scale preparation., (Copyright © 2024, Hao et al.)

Introduction: To examine changes in the prevalence of diabetes and the control of risk factors for diabetes over 10 years among adults in China., Methods: Two population-based cross-sectional surveys were used to obtain a nationally representative sample of adults aged 20 years and older in mainland China in 2007 (n = 46 239) and 2017 (n = 73 340). Changes in the prevalence of diabetes, impaired fasting glucose, impaired glucose tolerance, and prediabetes, as diagnosed by the World Health Organization criteria, were assessed over time., Results: The weighted prevalence of diagnosed diabetes (3.8% vs 6.3%, p = .0001) and total diabetes (9.7% vs 11.7%, p = .005) increased among the overall population between 2007 and 2017. The weighted prevalence of undiagnosed diabetes (5.9% vs 5.4%, p = .7), impaired fasting glucose (2.7% vs 2.6%, p = .68), impaired glucose tolerance (12.7% vs 12.5%, p = .95), prediabetes (15.4% vs 15.1%, p = .79), the treatment of diabetes (34.1% vs 32.5%, p = .44), and the control of diabetes (31.1% vs 32.8%, p = .73) did not significantly change over this period. The awareness of diabetes (39.4% vs 53.6%, p = .0004) increased over 10 years among the overall population. The proportion of achieved high-density lipoprotein cholesterol targets increased (p = .005), but the proportion of achieved body mass index (p = .01) and waist circumference (p = .0002) targets decreased significantly., Conclusions: Between 2007 and 2017, the prevalence of total diabetes (diagnosed by the World Health Organization criteria), especially diagnosed diabetes, increased among adults in China. Although awareness of diabetes improved, effective interventions and clinical strategies are urgently required., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Borna disease virus (BoDV-1) is a bornavirus prototype that infects the central nervous system of various animal species and can cause fatal encephalitis in various animals including humans. Among the reported anti-BoDV-1 treatments, favipiravir (T-705) is one of the best candidates since it has been shown to be effective in reducing various bornavirus titers in cell culture. However, T-705 effectiveness on BoDV-1 is cell type-dependent, and the molecular mechanisms that explain this cell type-dependent difference remain unknown. In this study, we noticed a fact that T-705 efficiently suppressed BoDV-1 in infected 293T cells, but not in infected SH-SY5Y cells, and sought to identify protein(s) responsible for this cell-type-dependent difference in T-705 efficacy. By comparing the transcriptomes of BoDV-1-infected 293T and SH-SY5Y cells, we identified heart- and neural crest derivatives-expressed protein 2 (HAND2) as a candidate involved in T-705 interference. HAND2 overexpression partly attenuated the inhibitory effect of T-705, whereas HAND2 knockdown enhanced this effect. We also demonstrated an interaction between T-705 and HAND2. Furthermore, T-705 impaired HAND2-mediated host gene expression. Because HAND2 is an essential transcriptional regulator of embryogenesis, T-705 may exhibit its adverse effects such as teratogenicity and embryotoxicity through the impairment of HAND2 function. This study provides novel insights into the molecular mechanisms underlying T-705 interference in some cell types and inspires the development of improved T-705 derivatives for the treatment of RNA viruses., 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 © 2024 Elsevier B.V. All rights reserved.)

Butterfly wings display rich phenotypic diversity and are associated with complex biological functions, thus serving as an important evolutionary system to address the genetic basis and evolution of phenotypic diversification. We review recent butterfly studies that revealed complex functions underlying diversified wing patterns and describe the genetic and environmental factors involved in wing pattern determinations. These factors lead to inter-specific divergence, genetic polymorphism, and phenotypic plasticity, which in many cases are decided by several key genes. We also summarize the research advances on gene co-option as an important origin of functional complexity and evolutionary novelty. These findings reveal a pattern of evolutionary innovation within a constrained developmental framework during butterfly wing morphogenesis, but further research is required to gain a systematic and comprehensive understanding., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cerebral aneurysms (CAs) are a significant cerebrovascular ailment with a multifaceted etiology influenced by various factors including heredity and environment. This study aimed to explore the possible link between different types of immune cells and the occurrence of CAs. Methods: We analyzed the connection between 731 immune cell signatures and the risk of CAs by using publicly available genetic data. The analysis included four immune features, specifically median brightness levels (MBL), proportionate cell (PC), definite cell (DC), and morphological attributes (MA). Mendelian randomization (MR) analysis was conducted using the instrumental variables (IVs) derived from the genetic variation linked to CAs. Results: After multiple test adjustment based on the FDR method, the inverse variance weighted (IVW) method revealed that 3 immune cell phenotypes were linked to the risk of CAs. These included CD45 on HLA DR+NK (odds ratio (OR), 1.116; 95% confidence interval (CI), 1.001-1.244; p = 0.0489), CX3CR1 on CD14 - CD16 - (OR, 0.973; 95% CI, 0.948-0.999; p = 0.0447). An immune cell phenotype CD16 - CD56 on NK was found to have a significant association with the risk of CAs in reverse MR study (OR, 0.950; 95% CI, 0.911-0.990; p = 0.0156). Conclusion: Our investigation has yielded findings that support a substantial genetic link between immune cells and CAs, thereby suggesting possible implications for future clinical interventions., 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 © 2024 Shi, Wang, Teng, Hou and Lin.)

Numerous studies have discussed the impact of cosolvents on the structure, dynamics, and stability of proteins in aqueous solutions. However, the dynamics of cosolvents in the protein-water-cosolvent ternary system is largely unexplored in experiments due to technical difficulty. Consequently, a comprehensive understanding of the interplay among proteins, water, and cosolvents is still lacking. Here, we employed selective deuteration and neutron scattering techniques to characterize the individual motions of each component in the protein/water/glycerol (GLY) mixture across various temperatures. The consistent dynamic onset temperatures and the correlation between the MSD of the protein and the viscosity of solvents revealed the mutual coupling effects among the three components. Furthermore, our experimental and simulation results showed that the hydrogen bond relaxation energy barrier in the ternary system is ∼43 kJ/mol, whereas in the protein-water binary system it is merely ∼35 kJ/mol. Therefore, we suggest that GLY can enhance hydrogen bond interactions in the ternary system through the mutual coupling effect, thereby serving as one of the protective mechanisms of protein preservation by GLY.

Objective: Long non-coding RNAs (lncRNAs) are of great importance in the process of colorectal cancer (CRC) tumorigenesis and progression. However, the functions and underlying molecular mechanisms of the majority of lncRNAs in CRC still lack clarity., Methods: A Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect lncRNA NUTM2A-AS1 expression in CRC cell lines. Cell counting kit 8 (CCK-8) assay and flow cytometry were used to examine the biological functions of lncRNA NUTM2A-AS1 in the proliferation and apoptosis of CRC cells. RT-qPCR and western blot were implemented for the detection of cell proliferation-, apoptosis-related proteins, and FAM3C. Bioinformatics analysis and dual- luciferase reporter assays were utilized to identify the mutual regulatory mechanism of ceRNAs., Results: lncRNA NUTM2A-AS1 notably elevated in CRC cell lines and the silenced of NUTM2A- AS1 declined proliferation and facilitated apoptosis. Mechanistically, NUTM2A-AS1 was transcriptionally activated by histone H3 on lysine 27 acetylation (H3K27ac) enriched at its promoter region, and NUTM2A-AS1 acted as a sponge for miR-126-5p, leading to the upregulation of FAM3C expression in CRC cell lines., Conclusion: Our research proposed NUTM2A-AS1 as an oncogenic lncRNA that facilitates CRC malignancy by upregulating FAM3C expression, which might provide new insight and a promising therapeutic target for the diagnosis and treatment of CRC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The effect of anti-osteoporosis treatment in elderly patients with osteoporosis and lumbar discectomy and fusion (LIF) for lumbar degenerative diseases is not well known., Objective: This study aimed to evaluate the effect of perioperative anti-osteoporosis treatment in the patients with osteoporosis and LIF., Methods: From January to December 2022, patients were divided into three groups according to the inclusive criteria: the normal group (Group A), the osteopenia group (Group B) and the osteoporosis group (Group C). Quantitative computed tomography (QCT), height of the intervertebral space (HIS), segmental sagittal angle (SSA), visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were compared between the groups at the follow-up time. The serum Ca2 + , osteocalcin (OC), propeptide of type I procollagen (PINP) C-terminal cross-linking telopeptide of type I collagen (β-CTX) and 25-OH vitamin D (25-OH VD) levels were compared between the groups at the time of follow-up. Interbody fusion was graded on the X-ray and CT images at the follow-up time., Results: There were 165 patients in this study. There were significant differences in the mean age, mean score, HIS and SSA between the groups at the different follow-up times. There were significant differences in the concentrations of serum Ca2 + , OC, β-CTX, 25-OH VD and PINP at the sixth month after surgery between the groups. There were significant differences in the concentrations of serum Ca2 + , β-CTX and 25-OH VD between the pre-surgery and at six months after surgery in Group B and β-CTX and 25-OH VD in Group C. There was a significant difference in the degree of fusion between Group B and C (χ2= 5.6243, P< 0.05)., Conclusion: In elderly patients with LIF and osteoporosis, anti-osteoporosis therapy could reduce bone resorption and thus facilitate fusion. Anti-osteoporosis medication tends to enhance radiological, functional, and fusion short-term outcomes.

Background and Aim: The anti-interleukin-23 antibody risankizumab is being investigated as a treatment for moderate-to-severe Crohn's disease. This post hoc subanalysis evaluates the efficacy and safety of risankizumab therapy in Asian patients., Methods: ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) were randomized, double-blind, placebo-controlled, phase 3 induction studies. Patients with intolerance/inadequate response to biologic (MOTIVATE) and/or conventional therapy (ADVANCE) were randomized to receive intravenous risankizumab (600 or 1200 mg) or placebo at weeks 0, 4, and 8. Clinical responders to risankizumab could enter the phase 3, randomized, double-blind, placebo-controlled maintenance withdrawal study (FORTIFY; NCT03105102). Patients were rerandomized to receive subcutaneous risankizumab (180 or 360 mg) or placebo (withdrawal) every 8 weeks for 52 weeks., Results: Among 198 Asian patients in the induction studies, clinical remission and endoscopic response at week 12 were achieved by 61.4% and 40.0%, 59.5% and 35.8%, and 27.3% and 9.1% of patients in the risankizumab 600 mg, risankizumab 1200 mg, and placebo groups, respectively. Among 67 patients who entered the maintenance study, clinical remission and endoscopic response at week 52 were achieved by 57.1% and 52.4%, 75.0% and 40.0%, and 53.8% and 34.6% of patients in the risankizumab 180 mg, risankizumab 360 mg, and placebo (withdrawal) groups, respectively. Fistula closure was observed with risankizumab treatment in 28.6% (induction) and 57.1% (maintenance) of patients. Efficacy trends and safety profile were similar to those in non-Asian patients., Conclusion: Consistent with non-Asian and global population results, risankizumab was effective and well tolerated in Asian patients with Crohn's disease., (© 2023 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Deep venous thrombosis (DVT) has a significant negative impact on surgical and tumor patient's safety and quality of life. There was no specific report on the incidence and risk factors of postoperative lower extremity DVT in cervical cancer patients. Analysis of the risk factors of postoperative DVT in patients with cervical cancer is of great clinical significance for prevention and treatment. We retrospectively analyzed 309 cervical cancer patients treated by the Hubei Cervical Cancer Prevention Center and used a logistic regression model to test the risk variables of postoperative lower extremity deep venous thrombosis in cervical cancer patients. By univariate analyses, the results of the study showed that the incidence of postoperative DVT was significantly increased in cervical cancer patients complicated with old age, obesity, high preoperative plasma D-dimer level, increased preoperative triglyceride level, chronic diseases (hypertension, diabetes, and cardiovascular disease), open surgery, long operation time, intraoperative blood transfusion, advanced tumor stage, and preoperative chemotherapy/radiotherapy. Advanced age, obesity, elevated preoperative D-dimer level, high preoperative triglyceride level, and open surgery were independent risk factors for postoperative lower extremity DVT in patients with cervical cancer by multivariate regression analyses (all P  < .05). In gynecologic patients with cervical cancer, there is a high incidence of postoperative lower extremity DVT. Clinicians should develop systematic and comprehensive prevention and treatment measures for the risk factors to lower this morbidity and improve patient prognosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ginseng ( Panax ginseng Mayer) is an important natural medicine. However, a long culture period and challenging quality control requirements limit its further use. Although artificial cultivation can yield a sustainable medicinal supply, research on the association between the transplantation and chaining of metabolic networks, especially the regulation of ginsenoside biosynthetic pathways, is limited., Methods: Herein, we performed Liquid chromatography tandem mass spectrometry based metabolomic measurements to evaluate ginsenoside accumulation and categorise differentially abundant metabolites (DAMs). Transcriptome measurements using an Illumina Platform were then conducted to probe the landscape of genetic alterations in ginseng at various ages in transplantation mode. Using pathway data and crosstalk DAMs obtained by MapMan, we constructed a metabolic profile of transplantation Ginseng., Results: Accumulation of active ingredients was not obvious during the first 4 years (in the field), but following transplantation, the ginsenoside content increased significantly from 6-8 years (in the wild). Glycerolipid metabolism and Glycerophospholipid metabolism were the most significant metabolic pathways, as Lipids and lipid-like molecule affected the yield of ginsenosides. Starch and sucrose were the most active metabolic pathways during transplantation Ginseng growth., Conclusion: This study expands our understanding of metabolic network features and the accumulation of specific compounds during different growth stages of this perennial herbaceous plant when growing in transplantation mode. The findings provide a basis for selecting the optimal transplanting time., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Background: Vitexicarpin (VIT), an isoflavone derived from various medicinal herbs, has shown promising anti-tumor activities against multiple cancer cells. However, the understanding of the mechanisms and potential targets of VIT in treating triple-negative breast cancer (TNBC) remains limited., Methods: The potential VIT targets were searched for in the Super-PRED online database, while the TNBC targets were acquired in the DisGeNET database, and the Veeny database was used to identify the VIT and TNBC targets that overlapped. Then, GO and KEGG enrichment analyses were carried out in the DAVID database. The protein-protein interaction (PPI) network was constructed to acquire the hub targets in the STRING database, and the overall survival analysis of the hub targets was examined in the Kaplan-Meier plotter database. Afterward, molecular docking was performed to evaluate the binding capabilities between VIT and the hub targets. In order to measure the effect of VIT on proliferation, apoptosis, and cell cycle arrest in the TNBC cell lines-MDA-MB-231 and HCC-1937-the Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis were performed. The Western blot and pull-down assays were used to verify the molecular mechanisms by modulating the hub targets., Results: The network pharmacology results identified a total of 37 overlapping genes that were shared by VIT and TNBC. The results of the PPI network and molecular docking analyses showed that HSP90AA1, CREBBP, and HIF-1A were key targets of VIT against TNBC. However, the pull-down results suggested that VIT could directly bind to HSP90AA1 and HIF-1A, yet not to CREBBP. The results of the in vitro tests showed that VIT decreased proliferation and induced apoptosis in MDA-MB-231 and HCC-1937 cells, in a dose-dependent manner, while the cell cycle arrest occurred at the G2 phase. Mechanistically, the Western blot assay demonstrated that VIT decreased the expression of HSP90AA1, CREBBP, and HIF-1A., Conclusions: VIT inhibited growth and induced apoptosis of TNBC cells by modulating HIF-1A, HSP90AA1, and CREBBP expression. Our findings suggest that VIT is a potential drug for TNBC therapy., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Author(s). Published by IMR Press.)

Non-computational classical evolution analysis of plectasin and its functional relatives can especially contribute tool value during access to meet requirements for their better druggability in clinical use. Staphylococcus aureus is a zoonotic pathogen that can infect the skin, blood, and other tissues of humans and animals. The impact of pathogens on humans is exacerbated by the crisis of drug resistance caused by the misuse of antibiotics. In this study, we analyzed the evolution of anti- Staphylococcus target functional sequences, designed a series of plectasin derivatives by truncation, and recombinantly expressed them in Pichia pastoris X-33, from which the best recombinant Ple-AB was selected for the druggability study. The amount of total protein reached 2.9 g/L following 120 h of high-density expression in a 5-L fermenter. Ple-AB was found to have good bactericidal activity against gram-positive bacteria, with minimum inhibitory concentration (MIC) values ranging between 2 and 16 μg/mL. It showed good stability and maintained its bactericidal activity during high temperatures, strong acid and alkali environments. Notably, Ple-AB exhibited better druggability, including excellent trypsin resistance, and still possessed approximately 50% of its initial activity following exposure to simulated intestinal fluids for 1 h. In vitro safety testing of Ple-AB revealed low hemolytic activity against mouse erythrocytes and cytotoxicity against murine-derived macrophages. This study successfully realized the high expression of a new antimicrobial peptide (AMP), Ple-AB, in P. pastoris and the establishment of its oral administration as an additive form with high trypsin resistance; the study also revealed its antibacterial properties, indicating that truncation design is a valuable tool for improving druggability and that the candidate Ple-AB may be a novel promising antimicrobial agent., 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 © 2023 Li, Hao, Yang, Mao, Teng and Wang.)

The marine peptide, American oyster defensin (AOD), is derived from Crassostrea virginica and exhibits a potent bactericidal effect. However, recombinant preparation has not been achieved due to the high charge and hydrophobicity. Although the traditional fusion tags such as Trx and SUMO shield the effects of target peptides on the host, their large molecular weight (12-20 kDa) leads to the yields lower than 20% of the fusion protein. In this study, a short and acidic fusion tag was employed with a compact structure of only 1 kDa. Following 72 h of induction in a 5 L fermenter, the supernatant exhibited a total protein concentration of 587 mg/L. The recombinant AOD was subsequently purified through affinity chromatography and enterokinase cleavage, resulting in the final yield of 216 mg/L and a purity exceeding 93%. The minimum inhibitory concentrations (MICs) of AOD against Staphylococcus aureus , Staphylococcus epidermidis , and Streptococcus galactis ranged from 4 to 8 μg/mL. Moreover, time-killing curves indicated that AOD achieved a bactericidal rate of 99.9% against the clinical strain S. epidermidis G-81 within 0.5 h at concentrations of 2× and 4× MIC. Additionally, the activity of AOD was unchanged after treatment with artificial gastric fluid and intestinal fluid for 4 h. Biocompatibility testing demonstrated that AOD, at a concentration of 128 μg/mL, exhibited a hemolysis rate of less than 0.5% and a cell survival rate of over 83%. Furthermore, AOD's in vivo therapeutic efficacy against mouse subcutaneous abscess revealed its capability to restrain bacterial proliferation and reduce bacterial load, surpassing that of antibiotic lincomycin. These findings indicate AOD's potential for clinical usage.

The Aphis gossypii is a major threat of cotton worldwide due to its short life cycle and rapid reproduction. Chemical control is the primary method used to manage the cotton aphid, which has significant environmental impacts. Therefore, prioritizing eco-friendly alternatives is essential for managing the cotton aphid. The ladybird, Hippodamia variegata , is a predominant predator of the cotton aphid. Its performance in cotton plantation is directly linked to chemical communication, where volatile compounds emitted from aphid-infested plants play important roles in successful predation. Here, we comprehensively studied the chemical interaction between the pest, natural enemy and host plants by analyzing the volatile profiles of aphid-infested cotton plants using gas chromatography-mass spectrometry (GC-MS). We then utilized the identified volatile compounds in electrophysiological recording (EAG) and behavioral assays. Through behavioral tests, we initially demonstrated the clear preference of both larvae and adults of H. variegata for aphid-infested plants. Subsequently, 13 compounds, namely α-pinene, cis -3-hexenyl acetate, 4-ethyl-1-octyn-3-ol, β-ocimene, dodecane, E-β-farnesene, decanal, methyl salicylate, β-caryophyllene, α-humulene, farnesol, DMNT, and TMTT were identified from aphid-infested plants. All these compounds were electrophysiologically active and induced detectable EAG responses in larvae and adults. Y-tube olfactometer assays indicated that, with few exceptions for larvae, all identified chemicals were attractive to H. variegata , particularly at the highest tested concentration (100 mg/ml). The outcomes of this study establish a practical foundation for developing attractants for H. variegata and open avenues for potential advancements in aphid management strategies by understanding the details of chemical communication at a tritrophic level., 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 © 2023 Yi, Teng, Xie, Tang, Zhao, Liu, Liu, Ding, Khashaveh and Zhang.)

Objective: The metabolic syndrome (MetS) is diagnosed upon the manifestation of ≥ 3 out of 5 specific components. The present study evaluated the epidemiological characteristics of the MetS components and their clustering condition among Chinese adults., Methods: 68383 participants aged 18-80 years from TIDE were scored on a six-point (0-5) MetS severity score (MSSS), which quantified their cumulative amount of MetS risk components. We evaluated the epidemiological characteristics of these components and their clustering conditions. Additionally, we examined the relation of age with the prevalence of different MSSSs or specific MetS components using restricted cubic splines., Results: Among 68383 participants, 26113 men and 24582 women had abnormal MetS components. There were significant differences in most epidemiological characteristics between the 6 MSSS groups. The top three prevalence of abnormal metabolic components were high systolic blood pressure (SBP) (9.41%, n=6568), high waist circumference (WC) (8.13%, n=6120), and the cooccurrence of high SBP and high WC (6.33%, n=4622). Participants were more likely to have all five MetS components when HDL-C was low. Restricted cubic splines showed that when the MSSS ≥3, the MetS prevalence of male peaked and that of the female population increased most rapidly at 40-60 age group., Conclusion: The 40-60 age group can be regarded as the high-risk period of MetS, and elderly women have a higher risk of multiple metabolic disorders than men. The top three clustering of abnormal metabolic components were high SBP, high WC, and their combination. Multiple components aggregation was more likely to occur when HDL-C decreased., 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 © 2023 Zhao, Lu, Song, Chen, Teng, Shan and Teng.)

The diagnosis of goiter is based on the thyroid volume measured by ultrasound in which iodine plays an important role. The purpose of this study was to evaluate the factors that affect thyroid volume and update the reference range of thyroid volume to provide a new basis for the diagnosis and treatment of goiter. A study population from mainland China was evaluated in the Thyroid disorders, Iodine status and Diabetes Epidemiological (TIDE) study. Thyroid size was measured by ultrasound, and thyroid volume was calculated. A quantile regression model was used to analyze the influence of related factors on the thyroid volume at each percentile. The median urinary iodine concentration (UIC) was 185.54 μg/l. The quantile regression model suggested that body surface area (BSA) and thyroid-stimulating hormone (TSH) were positive and negative factors for thyroid volume, respectively (p < 0.01). Excess iodine reduces the median and lower limits of thyroid volume. In iodine-sufficient areas, smoking is no longer a risk factor. The reference value range of thyroid volume stratified by sex was 3.92-19.06 ml for males and 3.1-16.17 ml for females. The maximum reference ranges for stratification by sex and BSA were 4.25-20.98 ml for men and 3.44-18.31 ml for women. The iodine nutrition level of the population in mainland China is sufficient. Iodine has the potential to alter the effect of certain factors on thyroid volume and effect is not regional. The new reference interval of adult thyroid volume based on sex and BSA has been updated, which can be used as a reliable reference for updating the diagnostic criteria of endemic goiter., (© 2023. The Author(s).)

The saturated flue gas is difficult to recover and use as low-grade waste heat in a coal-fired power plant. The absorption heat pump is important equipment for recovering low-grade waste heat. In this article, the saturated flue gas waste heat is recovered to reduce the turbine extraction steam of low-pressure heaters. The simulation system is built, and the operational characteristics are analyzed. The feasibility of saturated flue gas waste heat recovered is verified by the absorption heat pump to heat the boiler feedwater. The results show that generator pressure and throttle pressure have significant influence on the operational performance of the absorption heat pump. There is the risk of solution crystallization with the high-concentration dehumidification solution. The equivalent enthalpy drop of the extraction steam is lower in the higher number of heater stages, representing the weaker electricity generation capacity. The waste heat temperature of saturated flue gas can be raised by 30-40 °C, which is used as the low-grade heat source for the absorption heat pump. The feedwater of low-pressure heaters is heated by the absorption heat pump, and its temperature ranges from 59.2 to 83.8 °C. The simulation system can efficiently recover the waste heat of saturated flue gas up to 9.99 MW and achieve additional electricity generation up to 0.56 MW in the coal-fired power plant., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Pathogenic Escherichia coli is one of the most common causes of diarrhea diseases and its characteristic component of the outer membrane-lipopolysaccharide (LPS) is a major inducer of sepsis. Few drugs have been proven to kill bacteria and simultaneously neutralize LPS toxicity. Here, the chimeric peptides-R7, A7 and G7 were generated by connecting LBP14 (LPS-targeting domain) with L7 (killing domain) via different linkers to improve antibacterial and anti-inflammatory activities. Compared to parent LBP14-RKRR and L7, the antibacterial activity of R7 with a cleavable "RKRR" linker and the "LBP14-RKRR + L7" cocktail against Escherichia coli, Salmonella typhimurium and Staphylococcus aureus was increased by 2 ~ 4-fold. Both A7 and G7 with non-cleavable linkers almost lost antibacterial activity. The ability of R7 to neutralize LPS was markedly higher than that of LBP14-RKRR and L7. In vivo, R7 could be cleaved by furin in a time-dependent manner, and release L7 and LBP14-RKRR in serum. In vivo, R7 can enhance mouse survival more effectively than L7 and alleviate lung injuries by selective inhibition of the NF-κB signaling pathways and promoting higher IAP activity. It suggests that R7 may be promising dual-function candidates as antibacterial and anti-endotoxin agents., (© 2023. The Author(s).)

To effectively perform the reliability analysis of the flap deflection angle, the reliability analysis framework is developed by introducing fault logic and a data-driven model. Herein, the fault logic analysis is used to study the fault mechanism and filter out the characteristic fault parameters that can be used to collect input data for data-driven modelling; the data-driven modelling is employed to establish a reliability analysis model with a small amount of input data. Under this proposed framework, the improved dung beetle optimization algorithm for back propagation (IDBO-BP) method is developed to perform the reliability modelling of the flap deflection angle. To validate the effectiveness of the proposed framework, we study the fault logic of flap symmetry and establish a surrogate model of flap deflection based on the fault parameters and the IDBO-BP algorithm. According to the predicted results of the flap deflection angle, the reliability model based on the fault mechanism can reflect the actual flap motion. At the same time, the proposed IDBO-BP algorithm has excellent modelling and simulation property by comparing with other optimization algorithms. Thus, the efforts of this study provide a new solution to the problem of reliable analysis with uncertain fault parameters. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.

Lactoferrin is an iron-binding glycoprotein of the transferrin family that is found in most bodily fluids of mammals and has a variety of biological and beneficial functions, with great importance in health enhancement as a supplement for humans and other animals. More than 300 t of lactoferrin were produced in 2021, and this number is expected to grow yearly by 10% to 12%, to over 580 t in 2030. With new and important functions of lactoferrin being revealed and studied, focus on its industrial production and application is increasing accordingly. However, lactoferrin is mainly sourced from cheese whey or skim milk by cation-exchange column chromatography, which is a costly and low-quality method. A potential solution for lactoferrin global supply chain construction is proposed in this article as a complement to traditional routes of purification from whey or skim milk. The large-scale production of lactoferrin, mainly by recombinant yeast, mammal, and grain systems, as well as the market niche and product design, are discussed., (© 2023, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Current online transactions of aquatic products are often plagued by problems such as low efficiency, high platform supervision cost, insufficient trust and leakage of transaction data. Blockchain has been widely used in many different fields due to its decentralization, non-tampering and distributed data management. In order to resolve the existing problems, a blockchain-based aquatic product trading matching model integrated with credit mechanisms is proposed in this study to improve the efficiency, quality, security and satisfaction of online transactions for aquatic products. Then, based on this model, an online trading matching prototype system for aquatic products is developed, taking the Hyperledger Fabric as the underlying architecture. The performance testing of the prototype system has demonstrated that the introduction of the credit mechanism has a certain improvement effect on the trading matching results of aquatic products, and the system can complete more than 1000 transactions within half an hour, which can satisfy the normal business-to-business online transaction needs for aquatic products. To a certain extent, it can reduce the security risks and supervision cost, and improve the efficiency and satisfaction of online transaction. This study can also bring insights to blockchain-based online trading models in other industry fields.

Thyroid Stimulating Hormone (TSH) is a hormone secreted by the pituitary gland and plays a role in regulating the production and secretion of thyroid hormones by the thyroid gland. This precise feedback loop is essential for maintaining a harmonious balance of thyroid hormones in the body, which are vital for numerous physiological processes. Consequently, TSH serves as a significant marker in assessing thyroid function, and deviations from normal TSH levels may indicate the presence of a thyroid disorder. Thyroid cancer (TC) is the malignant tumor within the endocrine system. In recent years, numerous experts have dedicated their efforts to discovering efficacious biomarkers for TC. These biomarkers aim to improve the accurate identification of tumors with a poor prognosis, as well as facilitate active monitoring of tumors with a more favorable prognosis. The role of TSH in the thyroid gland underscores its potential influence on the occurrence and progression of TC, which has garnered attention in the scientific community. However, due to the limited scope of clinical research and the dearth of high-quality foundational studies, the precise impact of TSH on TC remains unclear. Consequently, we present a comprehensive review of this subject, aiming to offer a valuable reference for future research endeavors.

Background: Foam cells play crucial roles in all phases of atherosclerosis. However, until now, the specific mechanisms by which these foam cells contribute to atherosclerosis remain unclear. We aimed to identify novel foam cell biomarkers and interventional targets for atherosclerosis, characterizing their potential mechanisms in the progression of atherosclerosis., Methods: Microarray data of atherosclerosis and foam cells were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expression genes (DEGs) were screened using the "LIMMA" package in R software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were both carried out. Hub genes were found in Cytoscape after a protein-protein interaction (PPI) enrichment analysis was carried out. Validation of important genes in the GSE41571 dataset, cellular assays, and tissue samples., Results: A total of 407 DEGs in atherosclerosis and 219 DEGs in foam cells were identified, and the DEGs in atherosclerosis were mainly involved in cell proliferation and differentiation. CSF1R and PLAUR were identified as common hub genes and validated in GSE41571. In addition, we also found that the expression of CSF1R and PLAUR gradually increased with the accumulation of lipids and disease progression in cell and tissue experiments., Conclusion: CSF1R and PLAUR are key hub genes of foam cells and may play an important role in the biological process of atherosclerosis. These results advance our understanding of the mechanism behind atherosclerosis and potential therapeutic targets for future development., Competing Interests: The authors declare there are no competing interests., (©2023 Teng et al.)

Objective: To investigate the surgical efficacy of split liver transplantation. Methods: Patients who underwent liver transplantation at the Affiliated Hospital of Qingdao University between January 2015 and December 2022 were retrospectively analyzed. They were divided into split liver transplantation group ( n =60) and whole liver transplantation group ( n =765)according to graft types.In the split liver transplantation group, there were 23 males and 37 females, aged (52.5±10.2) years, and the body mass index was (22.4±3.3) kg/m 2 . In the whole liver transplantation group, there were 630 males and 135 females, aged (51.2±9.6) years, and body mass index was (24.5±3.7) kg/m 2 .The basic data of the two groups were matched 1∶1 using the propensity score matching method. The independent sample t test and χ 2 test were used to compare the intraoperative and postoperative recovery of the two groups of donors and recipients. The overall survival rate and the graft survival rate of the two groups were analyzed by Kaplan-Meier method and the cumulative survival rate was compared by the Log-rank test. Results: Fifty-one well-matched pairs of data with similar baseline characteristics were obtained. The ratio of graft mass to recipient body weight in the matched split liver transplantation group was (1.78±0.55)%. Operation time( M (IQR))(10.8(1.5)hours vs. 8.0(1.9)hours, U =6.608, P <0.01) and cold ischaemia time(5.4(1.3)hours vs. 4.6(2.2)hours, U =2.825, P =0.005) were significantly longer in the split liver transplantation group than those in the whole liver transplantation group. Intra-operative anhepatic phase(53.0(15.0)minutes vs. 57.0(24.0)minutes, U =1.048, P =0.295),bleeding volume(1 000(1 400)ml vs. 1 200(1 200)ml, U =0.966, P =0.334) and intraoperative instillation of red blood cells(9.0(6.5)U vs. 11.0(11.0)U, U =1.732, P =0.083) were not significantly different between the two groups. However,the split liver transplantation group showed significantly longer postoperative intensive care unit stay(5.0(3.0)days vs. 4.0(4.0)days, U =2.677, P =0.007) and postoperative hospital stay(30.0(15.0)days vs. 26.0(15.0)days, U =2.237, P =0.025) and significantly higher incidence of postoperative complications(56.8%(29/51) vs. 36.6%(19/51), χ 2 =3.935, P =0.047) than the whole liver transplantation group. Furthermore,levels of alanine transaminase and aspartate aminotransferase were significantly higher on postoperative days 1,4 and 7 in the split liver transplantation group(all P <0.05) than in the whole liver transplantation group;however,there were no significant differences in these levels on postoperative days 14 and 28. The time to restoration of normal liver function in both groups(12.5(13.7)days vs. 9.0(12.5)days, U =1.607, P =0.108) was not statistically significant. Furthermore,the median follow-up time after surgery was 25.6 months in both groups. In postoperative years 1,2,3 and 5, the graft survival rates were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,70.3%,67.3% and 60.5% in the split liver transplantation group( P =0.171),respectively. The patient survival rates in post-operative years 1,2,3 and 5 were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,75.9%,70.3% and 63.3% in the split liver transplantation group,respectively( P =0.252). However,the differences of graft survival rates and patient survival rates between the two groups were not significant. Conclusion: Although it affects the early recovery of patients after liver transplantation,split liver transplantation has no effect on long-term survival rates and demonstrates surgical efficacy similar to that of whole liver transplantation.

Most nonalcoholic steatohepatitis (NASH) patients develop severe fibrosis through extracellular matrix (ECM) accumulation, which can lead to hepatocellular carcinoma (HCC). Fibroblast growth factor 9 (FGF9) is involved in serial types of cancer; however, the specific role of FGF9 in NASH-driven HCC is not fully understood. This study finds that FGF9 is increased in patients with NASH-associated HCC. Furthermore, NASH-driven HCC mice models by feeding wildtype mice with high-fat/high-cholesterol (HFHC) diet and low dose carbon tetrachloride (CCl 4 ) treatment is established; and identified that hepatic FGF9 is increased; with severe fibrosis. Additionally, AAV-mediated knockdown of FGF9 reduced the hepatic tumor burden of NASH-driven HCC mice models. Hepatocyte-specific FGF9 transgenic mice (FGF9 Alb ) fed with a HFHC diet without CCl 4 treatment exhibited an increased hepatic ECM and tumor burden. However, XAV-939 treatment blocked ECM accumulation and NASH-driven HCC in FGF9 Alb mice fed with HFHC diet. Molecular mechanism studies show that FGF9 stimulated the expression of ECM related genes in a β-catenin dependent manner; and FGF9 exerts its effect on β-catenin stability via the ERK1/2-GSK-3β signaling pathway. In summary, the data provides evidence for the critical role of FGF9 in NASH-driven HCC pathogenesis; wherein it promotes the tumors formation through the ECM pathway., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Ultrasonic phased array imaging using full-matrix capture (FMC) has raised great interest among various communities, including the nondestructive testing community, as it makes full use of the echo space to provide preferable visualization performance of inhomogeneities. The conventional way of FMC data postprocessing for imaging is through beamforming approaches, such as delay-and-sum, which suffers from limited imaging resolution and contrast-to-noise ratio. To tackle these difficulties, we propose a deep learning (DL)-based image forming approach, termed FMC-Net, to reconstruct high-quality ultrasonic images directly from FMC data. Benefitting from the remarkable capability of DL to approximate nonlinear mapping, the developed FMC-Net automatically models the underlying nonlinear wave-matter interactions; thus, it is trained end-to-end to link the FMC data to the spatial distribution of the acoustic scattering coefficient of the inspected object. Specifically, the FMC-Net is an encoder-decoder architecture composed of multiscale residual modules that make local perception at different scales for the transmitter-receiver pair combinations in the FMC data. We numerically and experimentally compared the DL imaging results to the total focusing method and wavenumber algorithm and demonstrated that the proposed FMC-Net remarkably outperforms conventional methods in terms of exceeding resolution limit and visualizing subwavelength defects. It is expected that the proposed DL approach can benefit a variety of ultrasonic array imaging applications., (© 2023 Acoustical Society of America.)

It has been shown that SGLT2 suppresses atherosclerosis (AS). Recent studies indicate that autophagy widely participates in atherogenesis. This study aimed to assess the effect of canagliflozin (CAN) on atherogenesis via autophagy. Macrophages and ApoE - / - mice were used in this study. In macrophages, the results showed that CAN promoted LC3II expression and autophagosome formation. Furthermore, the cholesterol efflux assay demonstrated that CAN enhanced cholesterol efflux from macrophages via autophagy, resulting in lower lipid droplet concentrations in macrophages. The western blot revealed that CAN regulated autophagy via the AMPK/ULK1/Beclin1 signaling pathway. CAN resulted in increased macrophage autophagy in atherosclerotic plaques of ApoE - / - mice, confirming that CAN could inhibit the progression of AS via promoting macrophage autophagy. The current study found that CAN reduced the production of atherosclerotic lesions, which adds to our understanding of how SGLT2 inhibitors function to delay the progression of AS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Jasmonic acid (JA) and methyl jasmonate (MeJA), the crucial plant hormones, can induce the emission of plant volatiles and regulate the behavioral responses of insect pests or their natural enemies. In this study, two jasmonic acid carboxyl methyltransferases (JMTs), GhJMT1 and GhJMT2, involved in MeJA biosynthesis in Gossypium. hirsutum were identified and further functionally confirmed. In vitro , recombinant GhJMT1 and GhJMT2 were both responsible for the conversion of JA to MeJA. Quantitative real-time PCR (qPCR) measurement indicated that GhJMT1 and GhJMT2 were obviously up-regulated in leaves and stems of G. hirsutum after being treated with MeJA. In gas chromatography-mass spectrometry (GC-MS) analysis, MeJA treatment significantly induced plant volatiles emission such as ( E )-β-ocimene, ( Z )-3-hexenyl acetate, linalool and (3 E )-4,8-dimethyl-1,3,7-nonatriene (DMNT), which play vital roles in direct and indirect plant defenses. Moreover, antennae of parasitoid wasps Microplitis mediator showed electrophysiological responses to MeJA, β-ocimene, (Z) -3-hexenyl acetate and linalool at a dose dependent manner, while our previous research revealed that DMNT excites electrophysiological responses and behavioral tendencies. These findings provide a better understanding of MeJA biosynthesis and defense regulation in upland cotton, which lay a foundation to JA and MeJA employment in agricultural pest control., 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. The RE SN declared a shared affiliation with the author KHD to the handling editor at the time of review., (Copyright © 2023 Teng, Jing, Lv, Huang, Zhao, Kou, Liu, Dhiloo and Zhang.)

Objective: To explore and evaluate the clinical therapeutic effect of laparoscopic uterine artery pre-ligation combined with hysteroscopic curettage in the treatment of type II cesarean scar pregnancy., Methods: This study analyzed the clinical data of patients with cesarean scar pregnancy (CSP) in the Maternal and Child Health Hospital of Hubei Province from 2018 to 2022. A total of 134 patients with type II cesarean section were enrolled, out of which 78 patients were included in the final analysis. Treatment included either uterine artery embolization (UAE) combined with hysteroscopic curettage ( n = 37 patients) or laparoscopic uterine artery pre-ligation (LUAP) combined with hysteroscopic curettage ( n = 41 patients). The demographic and clinical characteristics of these two groups were recorded, and their short- and long-term complications on follow-up were compared. For patients with subsequent fertility requirements, we followed up these patients for 2 years after surgery, then collected and analyzed the compared subsequent pregnancy outcome., Results: We found no significant discrepancies in the success rate of operation, length of hospital stay, and intraoperative blood loss between the two different operation modes. The cost of LUAP was significantly lower than that of UAE. Furthermore, the incidence of short-term postoperative complications such as fever and pelvic pain was lower in patients treated with LUAP than in those treated with UAE. In terms of long-term postoperative complications, the recovery time for menstruation in the LUAP group (49.81 ± 11.47) was earlier than that in the UAE group (34.90 ± 7.41) ( p < 0.05). Additionally, 4.9% of patients in the LUAP group had decreased menstrual flow, while 59% of patients in the UAE group had a marked decrease in menstrual flow, and the incidence and severity of intrauterine adhesions were significantly lower in the LUAP group than in the UAE group( p < 0.05). Consistent with the aforementioned observations, patients treated with LUAP had better postoperative re-pregnancy outcomes than those treated with UAE., Conclusions: Based on the findings, LUAP combined with hysteroscopic curettage is a safe and effective surgical scheme for the treatment of type II CSPs. In addition, compared with UAE, LUAP is associated with a lower surgical cost, fewer short and long-term complications, and better postoperative pregnancy outcomes. Thus, it should be widely applied in patients with type II CSPs., 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 © 2023 Teng, Gao, Li, Meng, Shi and Shi.)

Although antimicrobial peptides (AMPs) have highly desirable intrinsic characteristics in their commercial product development as new antimicrobials, the limitations of AMPs from experimental to scale development include the low oral bioavailability, and high production costs due to inadequate in vitro/in vivo gene expression- and low scale. Plectasin has good bactericidal activity against Staphylococcus and Streptococcus , and the selective bactericidal activity greatly reduces the damage to the micro-ecosystem when applied in vivo. However, its expression level was relatively low (748.63 mg/L). In view of these situations, this study will optimize and modify the structure of Plectasin, hoping to obtain candidates with high expression, no/low toxicity, and maintain desirable antibacterial activity. Through sequence alignment, Plectasin was used as a template to introduce the degenerate bases, and the screening library was constructed. After three different levels of screening, the candidate sequence PN7 was obtained, and its total protein yield in the supernatant was 5.53 g/L, with the highest value so far for the variants or constructs from the same ancestor source. PN7 had strong activity against several species of Gram-positive bacteria (MIC value range 1~16 μg/mL). It was relatively stable in various conditions in vitro; in addition, the peptide showed no toxicity to mice for 1 week after intraperitoneal injection. Meanwhile, PN7 kills Staphylococcus aureus ATCC 43300 with a mode of a quicker (>99% S. aureus was killed within 2 h, whereas vancomycin at 2× MIC was 8 h.) and longer PAE period. The findings indicate that PN7 may be a novel promising antimicrobial agent, and this study also provides a model or an example for the design, modification, or reconstruction of novel AMPs and their derivatives.

Background: We aimed to assess the long-term effects of the transition in iodine status on the incidence of thyroid disorders over 20 years of follow-up. Methods: The original prospective cohort study, started in 1999 ( n  = 3761), classified three regions in north China based on iodine status (insufficient iodine, more than adequate iodine, and excessive iodine, respectively) for 5 years. Subsequently, participants were followed for up to another 15 years to assess the long-term effects of shifts to adequate iodine on the incidence of thyroid disorders. Panshan transitioned from insufficient to adequate iodine, and Huanghua transitioned from excessive to more than adequate iodine. Both regions were compared with Zhangwu, in which iodine status changed from more than adequate to adequate iodine (from 214 to 167.2 μg/L). A cluster sampling method was used to select participants in the three regions. Participants completed questionnaires and underwent thyroid ultrasonography. Urinary iodine concentrations (UICs), serum thyroid hormone concentration, and thyroid antibodies were measured. Results: When the iodine status changed from insufficient to adequate (with the median UIC increasing from 88 to 141.9 μg/L), the incidence density of subclinical hyperthyroidism, positive thyroperoxidase antibody, positive thyroglobulin antibody (TgAb), and goiter decreased significantly ( p  < 0.05 for all). Additionally, the cumulative incidence of subclinical hypothyroidism was significantly lower compared with the region where the iodine status changed from being more than adequate to adequate (1.9% vs. 6.0%, p  < 0.001). When the iodine status changed from excessive to more than adequate (median UIC from 634 to 266.7 μg/L), a significant decrease in the incidence density of subclinical hyperthyroidism, positive thyroid antibodies, positive TgAb, and goiter ( p  < 0.05 for all) were also found. However, an increase in thyroid nodule incidence density (17.26 vs. 28.25 per 1000 person-years, p  < 0.001) was seen. Conclusions: The incidence of thyroid disorders (except for thyroid nodules) stabilized or decreased among adults in the three communities from year 5 to year 15 of follow-up. Appropriate iodine fortification is safe and effective over the long term. Restoring urinary iodine to appropriate levels reduces population risk for thyroid disorders.

Weaning is a crucial period in the pig's life cycle, which is frequently followed by gastrointestinal (GI) infections, diarrhea and even death. This study focused on the impact of bovine lactoferrin (bLF) supplementation on the intestinal health of weaning piglets. Weaning piglets (Duroc × Landrace × Yorkshire, 23 days) were randomly allocated into four groups, which included negative control group (CON): basic diet; positive control group (ANT): basic diet + 20 mg/kg flavomycin + 100 mg/kg aureomycin; treatment group bLF-A: basic diet + 1 g/kg bLF; treatment group bLF-B: basic diet + 3 g/kg bLF. The result showed that dietary supplementation of bLF can improve growth performance and reduce diarrhea, which exhibits dose-dependency (P < 0.05). Compared with CON group, supplementation with bLF significantly improved immunity, and increased villus height and ratio of villus height/crypt depth at the small intestinal mucosa (P < 0.05). The mRNA expression of claudin-1, occludin and ZO-1 was greatly increased in the ileum of bLF group on days 7 and 14 (P < 0.05). Furthermore, the supplementation of bLF increased the abundance of Lactobacillus and Bifidobacterium and decreased the abundance of Escherichia coli in the cecum on day 7 (P < 0.05). The dietary supplementation of bLF enhanced the growth performance, reduced diarrhea rate in weaning piglets by improving intestinal immunity, morphology and barrier function, balancing intestinal microbiota. And bLF can be a promising feed additive in relieving stress situation of weaning piglets., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Human retinal organoid transplantation could potentially be a treatment for degenerative retinal diseases. How the recipient retina regulates the survival, maturation, and proliferation of transplanted organoid cells is unknown. We transplanted human retinal organoid-derived cells into photoreceptor-deficient mice and conducted histology and single-cell RNA sequencing alongside time-matched cultured retinal organoids. Unexpectedly, we observed human cells that migrated into all recipient retinal layers and traveled long distances. Using an unbiased approach, we identified these cells as astrocytes and brain/spinal cord-like neural precursors that were absent or rare in stage-matched cultured organoids. In contrast, retinal progenitor-derived rods and cones remained in the subretinal space, maturing more rapidly than those in the cultured controls. These data suggest that recipient microenvironment promotes the maturation of transplanted photoreceptors while inducing or facilitating the survival of migratory cell populations that are not normally derived from retinal progenitors. These findings have important implications for potential cell-based treatments of retinal diseases., Competing Interests: Conflict of interests M.S.S. is/was a paid advisor to Revision Therapeutics, Johnson & Johnson, Third Rock Ventures, Bayer Healthcare, Novartis Pharmaceuticals, W. L. Gore & Associates, Deerfield, Trinity Partners, Kala Pharmaceuticals, Janssen, and Acucela. M.S.S. has received sponsored research support from Bayer for other research. S.B. receives research support from Genentech, is a co-founder and shareholder in CDI Labs, LLC, and is/was a consultant for Third Rock Ventures and Tenpoint Therapeutics. M.S.S. and R.J.J are co-founders and shareholders in Agnos Therapeutics. These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies. M.S.S., S.B., J.Q., R.J.J., Y.V.L., C.P.S., M.V.C.-S., M.F.-B., S.A.-D., and K.V.L. are named as inventors on patents or patent applications assigned to their respective universities., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported., Objective: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment., Design: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients ( n  = 116)., Methods: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n  = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model., Results: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers., Conclusion: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment., Competing Interests: Dennis Teng is an employee of Abbvie, Inc. and may hold stock or stock options. The remaining co-authors have no competing interests to declare., (© The Author(s), 2023.)

Emotion talk (ET), an emotion socialization practice theorized to promote children's emotion understanding and emotion regulation, has been linked to better socioemotional adjustment in diverse samples. Immigrant children face developmentally unique challenges and opportunities related to their multi-lingual and multi-cultural experiences. The present study aimed to identify sociocultural correlates of parent ET in two groups of low-income immigrant families with preschool-age children: Mexican American (MA) and Chinese American (CA) families. In 90 parent-child dyads (child age = 38 to 70 months, 59% girls; 46 Mexican American and 44 Chinese American) recruited from Head Start programs, parents' (mostly mothers') ET quality and quantity (i.e., use of emotion words, emotion questions and explanations, and overall elaborateness of ET) were coded from verbal transcripts of a shared picture book reading task. First, we found similarities and differences in ET across the two groups. Both MA and CA parents used emotion words, emotion questions, and emotion reasoning, whereas linking the story to personal emotion experience was infrequent. MA parents used more negative emotion words, emotion reasoning, and engaged in more elaborate ET than CA parents. Second, we examined the unique relations of multiple socio-cultural factors (SES, cultural orientations, parent and child demographics) to parent ET. Parent education and child age were associated positively with emotion questions, income was associated positively with emotion reasoning, and parents' heritage culture orientation was associated positively with the elaborateness of ET. The findings highlight the need to consider socio-cultural variations in emotion socialization practices when adapting and disseminating socioemotional learning interventions.

AMP-activated protein kinase (AMPK) is a critical cellular energy sensor at the interface of metabolism and cancer. However, the role of AMPK in carcinogenesis remains unclear. Here, through analysis of the TCGA melanoma dataset, we found that PRKAA2 gene that encodes the α2 subunit of AMPK is mutated in ∼9% of cutaneous melanomas, and these mutations tend to co-occur with NF1 mutations. Knockout of AMPKα2 promoted anchorage-independent growth of NF1 -mutant melanoma cells, whereas ectopic expression of AMPKα2 inhibited their growth in soft agar assays. Moreover, loss of AMPKα2 accelerated tumor growth of NF1 -mutant melanoma and enhanced their brain metastasis in immune-deficient mice. Our findings support that AMPKα2 serves as a tumor suppressor in NF1 -mutant melanoma and suggest that AMPK could be a therapeutic target for treating melanoma brain metastasis., Competing Interests: M.A.D. has been a consultant to Roche/Genentech, Array, Pfizer, Novartis, BMS, GSK, Sanofi-Aventis, Vaccinex, Apexigen, Eisai, Iovance, Merck, and ABM Therapeutics, and he has been the PI of research grants to MD Anderson by Roche/Genentech, GSK, Sanofi-Aventis, Merck, Myriad, Oncothyreon, Pfizer, ABM Therapeutics, and LEAD Pharma. Y.N.V.G. has received funding from Calithera Biosciences., (© 2023 The Author(s).)

Background: Increased body mass index (BMI) and metabolic abnormalities both have potential associations with thyroid disease. The aim of this study was to investigate the correlation between different metabolic phenotypes of obesity and thyroid disorders using nationwide data from China., Methods: Data were collected from a cross-sectional survey called the Thyroid Disorders, Iodine Status, and Diabetes Epidemiological Survey conducted between 2015 and 2017 in China. A total of 69007 subjects aged 18 years or older were defined and divided into six groups on the basis of BMI and metabolic health status: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). We estimated the odds ratios (ORs) and confidence intervals [CIs] for different thyroid disorders according to metabolic phenotypes using multivariate logistic regression models., Results: In our study, we found that the prevalence of subclinical hypothyroidism was almost as high in the MUNW group as in the MUO group, the prevalence of overt hyperthyroidism was highest in the MUNW group and Graves' disease was highest in the MHO group. Our results also suggested that the prevalence of goiter and thyroid nodules increased with increased BMI values and that the MUO group had the highest incidence. Multivariate logistic regression analysis indicated that subjects with unhealthy metabolic phenotypes (MUNW, MUOW, and MUO) all had an increased risk of subclinical hypothyroidism, regardless of their BMI. MUNW subjects had an approximately 1.6-fold higher risk of overt hyperthyroidism and a 1.8-fold higher risk of Graves' disease than their metabolically healthy counterparts (MHNW). The present study also demonstrated that the MUO group had the highest risk of goiter and thyroid nodules among the metabolic phenotypes of obesity., Conclusion: Based on our study, we found that metabolic abnormalities and obesity play different roles in various thyroid diseases. Metabolically unhealthy individuals, both with and without obesity, have a higher risk of thyroid disorders than metabolically healthy individuals without obesity., 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 © 2023 Song, Lu, Teng, Shan and Teng.)

Pichia pastoris is the widely used expression system for producing recombinant secretory proteins. It is known that Kex2 protease plays a vital role in the process of protein secretion, in which the P1' site affects its cleavage efficiency. To enhance the expression level of fungal defensin-derived peptide NZ2114, this work attempts to optimize the P1' site of Kex2 by replacing it with 20 amino acids in turn. The results showed that when the amino acid of the P1' site was changed to Phe (F), the yield of target peptide significantly increased from 2.39 g/L to 4.81 g/L. Additionally, the novel peptide F-NZ2114 (short for FNZ) showed strong antimicrobial activity against Gram-positive (G + ) bacteria, especially for Staphylococcus aureus and Streptococcus agalactiae (MIC: 4-8 μg/mL). The FNZ was very stable and retained high activity in various conditions; in addition, a low cytotoxicity and no hemolysis were observed even at a high concentration of 128 μg/mL, and a longer postantibiotic effect was reached. The above results indicate that this engineering strategy provided a feasible optimization scheme for enhancing the expression level and druggability of this antimicrobial peptide from fungal defensin and other similar targets by this updated recombinant yeast.

Borna disease virus (BoDV-1) is a highly neurotropic RNA virus that causes neurobehavioral disturbances such as abnormal social activities and memory impairment. Although impairments in the neural circuits caused by BoDV-1 infection induce these disturbances, the molecular basis remains unclear. Furthermore, it is unknown whether anti-BoDV-1 treatments can attenuate BoDV-1-mediated transcriptomic changes in neuronal cells. In this study, we investigated the effects of BoDV-1 infection on neuronal differentiation and the transcriptome of differentiated neuronal cells using persistently BoDV-1-infected cells. Although BoDV-1 infection did not have a detectable effect on intracellular neuronal differentiation processes, differentiated neuronal cells exhibited transcriptomic changes in differentiation-related genes. Some of these transcriptomic changes, such as the decrease in the expression of apoptosis-related genes, were recovered by anti-BoDV-1 treatment, while alterations in the expression of other genes remained after treatment. We further demonstrated that a decrease in cell viability induced by differentiation processes in BoDV-1-infected cells can be relieved with anti-BoDV-1 treatment. This study provides fundamental information regarding transcriptomic changes after BoDV-1 infection and the treatment in neuronal cells.

Study Objective: To evaluate the effectiveness and safety of ultrasound-guided percutaneous microwave ablation (MWA) for a single uterine fibroid greater than 300 cm 3 ., Design: Retrospective observational study., Setting: China-Japan Union Hospital of Jilin University, China., Patients: Thirty-seven patients each with a single fibroid greater than 300 cm 3 diagnosed by ultrasound and core needle biopsy., Interventions: Ultrasound-guided percutaneous MWA., Measurements and Main Results: All patients were followed up for 12 months postoperatively to assess the postoperative lesion volume reduction rate, degree of symptomatic relief, improvements in quality of life, and occurrence of adverse events. All 37 patients met the criteria for complete ablation, and the lesion volume significantly decreased from 334.28 cm 3 (95% confidence interval [CI] 326.75-366.73) preoperatively to 52.01 cm 3 (95% CI, 46.95-74.69) at the 12-month follow-up (difference: 280.15 cm 3 ; 95% CI, 267.92-294.65; p <.001). The lesion volume reduction rates at 1, 3, 6, and 12 months postoperatively were 27.30% (95% CI, 24.12-31.45), 52.90% (95% CI, 47.95-55.80), 67.90% (95% CI, 63.03-70.77), and 84.00% (95% CI, 80.22-85.94), respectively. The differences in the preoperative and postoperative Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire scores were significant (p <.01). The hemoglobin levels of the anemic patients were significantly elevated after the procedure (p <.001). Of the 37 patients in this study, 29 patients (78.38%) had a highly significant treatment effect, and 8 patients (21.62%) had a significant treatment effect. Seventeen patients (45.95%) had Society of Interventional Radiology grade A to B adverse effects that required no clinical intervention or only simple clinical intervention., Conclusion: Ultrasound-guided percutaneous MWA has good clinical efficacy and high safety in the treatment of a single uterine fibroid greater than 300 cm 3 ., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the value of contrast-enhanced ultrasound (CEUS) combined with feeding artery ablation in the microwave ablation (MWA) of large solid benign thyroid nodules (LSBTNs) with a diameter ≥ 4 cm., Methods: We retrospectively analyzed 122 patients with LSBTN ≥ 4 cm in diameter treated with MWA. During evaluations before and after MWA, 53 patients who underwent conventional ultrasound examination were classified as the routine group, and 69 patients who underwent CEUS combined with feeding artery ablation were classified as the union group. The differences in ablation energy required per milliliter (AERPM), complication rate, regrowth rate, and volume reduction rate (VRR) were compared between the two groups., Results: The AERPM of the union group was significantly less than that of the routine group (956.3 ± 38.5 J/mL vs. 1025.9 ± 121.5 J/mL, p < 0.001). The complication rate of the routine group was significantly higher than that of the union group (13.2% vs. 2.9%, p = 0.031). The regrowth rate of the routine group (22.6%, 12/53) was significantly higher than that of the union group (7.2%, 5/69) (p = 0.015). At the 1st, 3rd, 6th, 12th, 18th, and 24th month after ablation, the mean VRRs of the routine group were significantly less than those of the union group, with p values of < 0.001, < 0.001, 0.002, 0.007, 0.013, and < 0.001, respectively., Conclusions: The application of CEUS combined with feeding artery ablation in the MWA of LSBTNs is helpful to reduce the regrowth rate, improve the ablation efficiency, and reduce bleeding., Key Points: • CEUS combined with feeding artery ablation in MWA of LSBTNs is helpful to reduce regrowth rate. • CEUS combined with feeding artery ablation can help improve ablation efficiency than conventional ultrasound in LSBTNs. • CEUS combined with feeding artery ablation helps reduce the incidence of bleeding during MWA., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20-40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research., (© 2023. The Author(s).)

Vergence-accommodation-conflict-free super multi-view (SMV) display based on more than one near-eye pinhole group for each pupil of the viewer is developed in this paper. Two-dimensionally arranged pinholes of a group correspond to different subscreens of the display screen, with perspective views projected by each subscreen through a corresponding pinhole splicing into an image of enlarged field of view (FOV). By sequentially switching on/off different pinhole groups, more than one mosaic image is projected to each pupil of the viewer. Adjacent pinholes of a group are endowed with different timing-polarizing characteristics to generate an effective noise-free region for each pupil. In the experiment, four groups of 3×3 pinholes are configured for a proof-of-concept SMV display on a 240 Hz display screen, with a diagonal FOV of 55 deg and a depth of field reaching 1.2 m.

Chitosan (CS) is a natural and low-cost adsorbent for capturing metal ions and organic compounds. However, the high solubility of CS in acidic solution would make it difficult to recycle the adsorbent from the liquid phase. In this study, the CS/Fe 3 O 4 was prepared via Fe 3 O 4 nanoparticles immobilized onto a CS surface, and the DCS/Fe 3 O 4 -Cu was further fabricated after surface modification and the adsorption of Cu ions. The meticulously tailored material displayed the sub-micron size of an agglomerated structure with numerous magnetic Fe 3 O 4 nanoparticles. During the adsorption of methyl orange (MO), the DCS/Fe 3 O 4 -Cu delivered a superior removal efficiency of 96.4% at 40 min, which is more than twice the removal efficiency of 38.7% for pristine CS/Fe 3 O 4 . At an initial MO concentration of 100 mg L -1 , the DCS/Fe 3 O 4 -Cu exhibited the maximum adsorption capacity of 144.60 mg g -1 . The experimental data were well explained by the pseudo-second-order model and Langmuir isotherm, suggesting the dominant monolayer adsorption. The composite adsorbent still maintained a large removal rate of 93.5% after five regeneration cycles. This work develops an effective strategy to simultaneously achieve high adsorption performance and convenient recyclability for wastewater treatment.

Objectives: To investigate the prevalence and risk factors of hypothyroidism after universal salt iodisation for 20 years in mainland China., Design: Nationwide, cross-sectional survey., Setting and Participants: The Thyroid Disorders, Iodine Status and Diabetes epidemiological study included adults from 31 provinces of China. Data included demographic, physical characteristics, urine, serum thyroid-stimulating hormone (TSH), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and thyroid ultrasonography. Subclinical hypothyroidism (SCH) was classified into severe SCH (TSH >10 mU/L) and mild SCH (TSH 4.2-9.9 mU/L). A total of 78 470 (38 182 men and 40 288 women) participants were included in the final analysis., Results: The prevalence of hypothyroidism was 13.95%. The prevalence rates of overt hypothyroidism (OH) and SCH were 1.02% and 13.93%, which mild SCH was significantly higher than severe SCH (12.18% vs 0.75%). Prevalence was higher in women than in men, and this gender difference was noted among all age groups. The prevalence of mild SCH, severe SCH and OH increases by 1.16%, 1.40% and 1.29% for every 10 years older. TPOAb or/and TgAb positive were significantly associated with OH and severe SCH (OR 15.9, p<0.001). However, SCH was positively correlated with increased urine iodine concentration, but this correlation was only in antibody-negative female patients. In non-autoimmune and male populations, there was a U-shaped relationship between severe SCH and OH and urine iodine concentration., Conclusions: Mild SCH is the most common form of hypothyroidism, which is related to iodine intake. Severe SCH is more similar to OH which autoimmune is the main cause. The various effects of iodine on hypothyroidism depend on thyroid autoimmune and gender., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

With the accelerating growth of antimicrobial resistance (AMR), there is an urgent need for new antimicrobial agents with low or no AMR. Antimicrobial peptides (AMPs) have been extensively studied as alternatives to antibiotics (ATAs). Coupled with the new generation of high-throughput technology for AMP mining, the number of derivatives has increased dramatically, but manual running is time-consuming and laborious. Therefore, it is necessary to establish databases that combine computer algorithms to summarize, analyze, and design new AMPs. A number of AMP databases have already been established, such as the Antimicrobial Peptides Database (APD), the Collection of Antimicrobial Peptides (CAMP), the Database of Antimicrobial Activity and Structure of Peptides (DBAASP), and the Database of Antimicrobial Peptides (dbAMPs). These four AMP databases are comprehensive and are widely used. This review aims to cover the construction, evolution, characteristic function, prediction, and design of these four AMP databases. It also offers ideas for the improvement and application of these databases based on merging the various advantages of these four peptide libraries. This review promotes research and development into new AMPs and lays their foundation in the fields of druggability and clinical precision treatment.