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Significance: Musculoskeletal diseases seriously affect global health, but their importance is greatly underestimated. These diseases often afflict the elderly, leading to disability, paralysis, and other complications. Hydrogen sulfide (H2S) plays an important role in the occurrence and development of musculoskeletal diseases, which may have potential ther-apeutic significance for these diseases., Recent Advances: Recently, it has been found that many musculoskeletal diseases, such as osteoporosis, periodontitis, muscle atrophy, muscle ischemia-reperfusion injury, mus-cle contraction under high fever, arthritis, and disc herniation, can be alleviated by sup-plementing H2S. H2S may be conducive to the development of multiple myeloma. The mechanism of H2S effect on the musculoskeletal system has been elucidated. A variety of H2S donors and nano-delivery systems provide prospects for H2S-based therapies., Critical Issues: Related research remains at the level of cell or animal experiments, and clinical research is lacking. The role of H2S in more musculoskeletal disorders remains largely unknown. The importance of musculoskeletal diseases has not been widely con-cerned. Targeted delivery of H2S remains a challenging task., Future Direction: Develop therapeutic drugs for musculoskeletal diseases based on H2S and test their safety, efficacy, and tolerance. Explore the combination of current musculo-skeletal disease drugs with H2S releasing components to improve efficacy and avoid side effects. Carry out relevant clinical trials to verify the possibility of its widespread use.

The mutual regulation between hydrogen sulfide (H 2 S) and microRNA (miRNA) is involved in the development of many diseases, including cancer, cardiovascular disease, inflammatory disease, and high-risk pregnancy. Abnormal expressions of endogenous H 2 S-producing enzyme and miRNA in tissues and cells often indicate the occurrence of diseases, so the maintenance of their normal levels in the body can mitigate damages caused by various factors. Many studies have found that H 2 S can promote the migration, invasion, and proliferation of cancer cells by regulating the expression of miRNA, while many H 2 S donors can inhibit cancer progression by interfering with the proliferation, apoptosis, cell cycle, metastasis, and angiogenesis of cancer cells. Furthermore, the mutual regulation between H 2 S and miRNA can also prevent cell injury in cardiovascular disease and inflammatory disease through anti-inflammation, anti-oxidation, anti-apoptosis, and pro-autophagy. In addition, H 2 S can promote angiogenesis and relieve vasoconstriction by regulating the expression of miRNA, thereby improving fetal growth in high-risk pregnancy. In this review, we discuss the mechanism of mutual regulation between H 2 S and miRNA in various diseases, which may provide reliable therapeutic targets for these diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cystathionine β-synthase (CBS) occupies a key position as the initiating and rate-limiting enzyme in the sulfur transfer pathway and plays a vital role in health and disease. CBS is responsible for regulating the metabolism of cysteine, the precursor of glutathione (GSH), an important antioxidant in the body. Additionally, CBS is one of the three enzymes that produce hydrogen sulfide (H 2 S) in mammals through a variety of mechanisms. The dysregulation of CBS expression in cancer cells affects H 2 S production through direct or indirect pathways, thereby influencing cancer growth and metastasis by inducing angiogenesis, facilitating proliferation, migration, and invasion, modulating cellular energy metabolism, promoting cell cycle progression, and inhibiting apoptosis. It is noteworthy that CBS expression exhibits complex changes in different cancer models. In this paper, we focus on the CBS synthesis and metabolism, tissue distribution, potential mechanisms influencing tumor growth, and relevant signaling pathways. We also discuss the impact of pharmacological CBS inhibitors and silencing CBS in preclinical cancer models, supporting their potential as targeted cancer therapies., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hydrogen sulfide (H 2 S), an endogenous gasotransmitter, plays a key role in several critical physiological and pathological processes in vivo, including vasodilation, anti-infection, anti-tumor, anti-inflammation, and angiogenesis. In colorectal cancer (CRC), aberrant overexpression of H 2 S-producing enzymes has been observed. Due to the important role of H 2 S in the proliferation, growth, and death of cancer cells, H 2 S can serve as a potential target for cancer therapy. In this review, we thoroughly analyzed the underlying mechanism of action of H 2 S in CRC from the following aspects: the synthesis and catabolism of H 2 S in CRC cells and its effect on cell signal transduction pathways; the inhibition effects of exogenous H 2 S donors with different concentrations on the growth of CRC cells and the underlying mechanism of H 2 S in garlic and other natural products. Furthermore, we elucidate the expression characteristics of H 2 S in CRC and construct a comprehensive H 2 S-related signaling pathway network, which has important basic and practical significance for promoting the clinical research of H 2 S-related drugs., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hydrogen sulfide (H 2 S), together with carbon monoxide (CO) and nitric oxide (NO), is recognized as a vital gasotransmitter. H 2 S is biosynthesized by enzymatic pathways in the skin and exerts significant physiological effects on a variety of biological processes, such as apoptosis, modulation of inflammation, cellular proliferation, and regulation of vasodilation. As a major health problem, dermatological diseases affect a large proportion of the population every day. It is urgent to design and develop effective drugs to deal with dermatological diseases. Dermatological diseases can arise from a multitude of etiologies, including neoplastic growth, infectious agents, and inflammatory processes. The abnormal metabolism of H 2 S is associated with many dermatological diseases, such as melanoma, fibrotic diseases, and psoriasis, suggesting its therapeutic potential in the treatment of these diseases. In addition, therapies based on H 2 S donors are being developed to treat some of these conditions. In the review, we discuss recent advances in the function of H 2 S in normal skin, the role of altering H 2 S metabolism in dermatological diseases, and the therapeutic potential of diverse H 2 S donors for the treatment of dermatological diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gasotransmitters are endogenous gaseous signaling molecules that can freely pass through cell membranes and transmit signals between cells, playing multiple roles in cell signal transduction. Due to extensive and ongoing research in this field, we have successfully identified many gasotransmitters so far, among which nitric oxide, carbon monoxide, and hydrogen sulfide are best studied. Gasotransmitters are implicated in various diseases related to necroptosis, such as cardiovascular diseases, inflammation, ischemia-reperfusion, infectious diseases, and neurological diseases. However, the mechanisms of their effects on necroptosis are not fully understood. This review focuses on endogenous gasotransmitter synthesis and metabolism and discusses their roles in necroptosis, aiming to offer new insights for the therapeutic approaches to necroptosis-associated diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Significance: Ferroptosis, a form of regulated cell death characterized by a large amount of lipid peroxidation-mediated membrane damage, joins the evolution of multisystem diseases, for instance, neurodegenerative diseases, chronic obstructive pulmonary disease, acute respiratory distress syndrome, osteoporosis, osteoarthritis, and so forth. Since being identified as the third gasotransmitter in living organisms, the intricate role of hydrogen sulfide (H 2 S) in ferroptosis has emerged at the forefront of research. Recent Advances: Novel targets in the relevant metabolic pathways have been found, including transferrin receptor 1, cystine/glutamate antiporter, and others, coupled with the exploration of new signaling pathways, particularly the p53 signaling pathway, the nitric oxide/nuclear factor erythroid 2-related factor 2 signaling pathway, and so on. Many diseases such as emphysema and airway inflammation, myocardial diseases, endothelial dysfunction in aging arteries, and traumatic brain injury have recently been found to be alleviated directly by H 2 S inhibition of ferroptosis. Safe, effective, and tolerable novel H 2 S donors have been developed and have shown promising results in phase I clinical trials. Critical Issues: Complicated cross talk between the ferroptosis signaling pathway and oncogenic factors results in the risk of cancer when inhibiting ferroptosis. Notably, targeted delivery of H 2 S is still a challenging task. Future Directions: Discovering more reliable and stable novel H 2 S donors and achieving their targeted delivery will enable further clinical trials for diseases associated with ferroptosis inhibition by H 2 S, determining their safety, efficacy, and tolerance.

In the past, hydrogen sulfide (H 2 S) was recognized as a toxic and dangerous gas; in recent years, with increased research, we have discovered that H 2 S can act as an endogenous regulatory transmitter. In mammals, H 2 S-catalyzing enzymes, such as cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, are differentially expressed in a variety of tissues and affect a variety of biological functions, such as transcriptional and posttranslational modification of genes, activation of signaling pathways in the cell, and metabolic processes in tissues, by producing H 2 S. Various preclinical studies have shown that H 2 S affects physiological and pathological processes in the body. However, a detailed systematic summary of these roles in health and disease is lacking. Therefore, this review provides a thorough overview of the physiological roles of H 2 S in different systems and the diseases associated with disorders of H 2 S metabolism, such as ischemia-reperfusion injury, hypertension, neurodegenerative diseases, inflammatory bowel disease, and cancer. Meanwhile, this paper also introduces H 2 S donors and novel release modes, as well as the latest preclinical experimental results, aiming to provide researchers with new ideas to discover new diagnostic targets and therapeutic options., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

In recent years, the impact of age-related diseases on human health has become increasingly severe, and developing effective drugs to deal with these diseases has become an urgent task. Considering the essential regulatory role of hydrogen sulfide (H 2 S) in these diseases, it is regarded as a promising target for treatment. H 2 S is a novel gaseous transmitter involved in many critical physiological activities, including anti-oxidation, anti-inflammation, and angiogenesis. H 2 S also regulates cell activities such as cell proliferation, migration, invasion, apoptosis, and autophagy. These regulatory effects of H 2 S contribute to relieving and treating age-related diseases. In this review, we mainly focus on the pathogenesis and treatment prospects of H 2 S in regulating age-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the integrative effects and mechanisms of transcutaneous electrical acustimulation (TEA) on postprocedural recovery from endoscopic retrograde cholangio-pancreatography (ERCP)., Materials and Methods: A total of 86 patients for elective ERCP were randomly ordered to receive TEA (n = 43) at acupoints PC6 and ST36 or Sham-TEA (n = 43) at sham points from 24 hours before ERCP (pre-ERCP) to 24 hours after ERCP (PE24). Scores of gastrointestinal (GI) motility-related symptoms and abdominal pain, gastric slow waves, and autonomic functions were recorded through the spectral analysis of heart rate variability; meanwhile, circulatory levels of inflammation cytokines of tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 and GI hormones of motilin, ghrelin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) were assessed by enzyme-linked immunosorbent assay., Results: 1) TEA, but not Sham-TEA, decreased the post-ERCP GI motility-related symptom score (2.4 ± 2.6 vs 7.9 ± 4.6, p < 0.001) and abdominal pain score (0.5 ± 0.7 vs 4.1 ± 2.7, p < 0.001) at PE24, and decreased the post-ERCP hospital day by 20.0% (p ＜0.05 vs Sham-TEA); 2) TEA improved the average gastric percentage of normal slow waves and dominant frequency by 34.6% and 33.3% at PE24, respectively (both p < 0.001 vs Sham-TEA); 3) TEA, but not Sham-TEA, reversed the ERCP-induced increase of TNF-α but not IL-10 at PE24, reflected as a significantly lower level of TNF-α in the TEA group than in the Sham-TEA group (1.6 ± 0.5 pg/mL vs 2.1 ± 0.9 pg/mL, p ＜ 0.01); 4) compared with Sham-TEA, TEA increased vagal activity by 37.5% (p ＜ 0.001); and 5) TEA caused a significantly higher plasma level of ghrelin (1.5 ± 0.8 ng/ml vs 1.1 ± 0.7 ng/ml, p ＜ 0.05) but not motilin, VIP, or CCK than did Sham-TEA at PE24., Conclusion: TEA at PC6 and ST36 accelerates the post-ERCP recovery, reflected as the improvement in GI motility and amelioration of abdominal pain, and suppression of the inflammatory cytokine TNF-α may mediate through both autonomic and ghrelin-related mechanisms., Competing Interests: Conflict of Interest The authors report no conflict of interest., (Copyright © 2024 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the levels of regulatory T cells (Tregs) and cytokines IL-35, TGF-β and IL-10 in peripheral blood of hemophilia A(HA) patients with FⅧ inhibitor and their clinical significance., Methods: 43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected, including 6 cases with FⅧ inhibitor and 37 cases without FⅧ inhibitor. In addition, 20 healthy males who underwent physical examinations were selected as healthy controls. Flow cytometry was used to detect the levels of CD4 + CD25 + CD127 - Tregs in peripheral blood of the HA patients and healthy controls, and ELISA assay was used to detect the expression levels of IL-35, TGF-β and IL-10 in serum, and their differences between different groups were compared., Results: Compared with the healthy control group, the level of Tregs in HA patients was decreased, and the level of Tregs in the FⅧ inhibitor positive group was the lowest, the difference was statistically significant ( P <0.05). There was no significant difference in the expression level of Tregs in HA patients of different severity levels. The serum IL-35, TGF-β, and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group, and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group (all P <0.05)., Conclusion: The decrease of Tregs, IL-35, TGF-β, and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

Dental Implants are expected to possess both excellent osteointegration and antibacterial activity because poor osseointegration and infection are two major causes of titanium implant failure. In this study, we constructed layer-by-layer self-assembly films consisting of anionic casein phosphopeptides-amorphous calcium phosphate (CPP-ACP) and cationic poly (L-lysine) (PLL) on sandblasted and acid etched (SLA) titanium surfaces and evaluated their osseointegration and antibacterial performance in vitro and in vivo. The surface properties were examined, including microstructure, elemental composition, wettability, and Ca 2+ ion release. The impact the surfaces had on the adhesion, proliferation and differentiation abilities of MC3T3-E1 cells were investigated, as well as the material's antibacterial performance after exposure to the oral microorganisms such as Porphyromonas gingivalis (P. g) and Actinobacillus actinomycetemcomitans (A. a). For the in vivo studies, SLA and Ti (PLL/CA-3.0) 10 implants were inserted into the extraction socket immediately after extracting the rabbit mandibular anterior teeth with or without exposure to mixed bacteria solution (P. g & A. a). Three rabbits in each group were sacrificed to collect samples at 2, 4, and 6 weeks of post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the implant osseointegration. The modified titanium surfaces were successfully prepared and appeared as a compact nano-structure with high hydrophilicity. In particular, the Ti (PLL/CA-3.0) 10 surface was able to continuously release Ca 2+ ions. From the in vitro and in vivo studies, the modified titanium surfaces expressed enhanced osteogenic and antibacterial properties. Hence, the PLL/CPP-ACP multilayer coating on titanium surfaces was constructed via a layer-by-layer self-assembly technology, possibly improving the biofunctionalization of Ti-based dental implants., 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.)

Hydrogen sulfide (H 2 S) is one of the three most crucial gaseous messengers in the body. The discovery of H 2 S donors, coupled with its endogenous synthesis capability, has sparked hope for the treatment of hematologic malignancies. In the last decade, the investigation into the impact of H 2 S has expanded, particularly within the fields of cardiovascular function, inflammation, infection, and neuromodulation. Hematologic malignancies refer to a diverse group of cancers originating from abnormal proliferation and differentiation of blood-forming cells, including leukemia, lymphoma, and myeloma. In this review, we delve deeply into the complex interrelation between H 2 S and hematologic malignancies. In addition, we comprehensively elucidate the intricate molecular mechanisms by which both H 2 S and its donors intricately modulate the progression of tumor growth. Furthermore, we systematically examine their impact on pivotal aspects, encompassing the proliferation, invasion, and migration capacities of hematologic malignancies. Therefore, this review may contribute novel insights to our understanding of the prospective therapeutic significance of H 2 S and its donors within the realm of hematologic malignancies., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although recent studies increasingly suggest the potential anti-cancer effect of quercetin, the exact underlying mechanism remains poorly demonstrated in oral squamous cell carcinoma (oSCC). Therefore, our research explored the impacts of quercetin on the ferroptosis and mTOR/S6KP70 axis in oSCC cell lines. After treating oSCC cells with quercetin or indicated compounds and transfection with SLC7A11- or S6KP70-overexpressing plasmid, cell viability was detected by CCK-8 assay. The level of ferroptosis in oSCC cells was assessed by measuring ROS and GSH levels. The activation of mTOR/S6KP70 axis was assessed by Western blotting. Quercetin promoted ferroptosis in an mTOR/S6KP70-dependent manner to inhibit tumor growth in oSCC cells. Mechanistically, we revealed that quercetin induced lipid peroxidation and reduced GSH levels by repressing SLC7A11 expression in oSCC cells. Specifically, the effects of quercetin on ferroptosis and mTOR and S6KP70 phosphorylation were partially blocked by both mTOR agonist and S6KP70 overexpression. Moreover, mTOR inhibitor promoted ferroptosis in quercetin-treated oSCC cells. Our findings showed that ferroptosis may be a new anti-tumor mechanism of quercetin. Additionally, we identified that quercetin can target mTOR/S6KP70 cascade to inhibit the growth of oSCC cells.

In this experiment, the micro-precipitation method was used to prepare self-assembled nanoparticles of Herpetospermum caudigerum Wall.(MP-SAN). The process was optimized using average particle size and polydispersity index(PDI)as evaluation indexes. The mean particle size, PDI,zeta potential, and microstructure of MP-SAN were characterized. The intestinal absorption mechanism of dehydrodiconiferyl alcohol(DA)and herpetrione(Her)in MP-SAN was investigated through single-pass intestinal perfusion in rats. The optimized process parameters for producing MP-SAN were a stirring speed of 800 r·min~(-1),stirring time of 5 min, and rotary evaporation temperature of 40℃. The resulting MP-SAN exhibited a spherical-like structure and uniform morphology, with a mean particle size of(267.63±13.27) nm, a PDI of 0.062 0±0.043 9,and a zeta potential of(-46.18±3.66) mV. The absorption rate constant(K&#95;a)and apparent permeability coefficient(P&#95;(app))of DA in the ileal segment were significantly higher than those in the jejunal segment(P&lt;0.05). However, there was no significant difference in the absorption of Her between the ileal and jejunal segments. Intestinal absorption parameters of DA and Her tended to increase with increasing drug concentration. Specifically, the K&#95;a and P&#95;(app) of DA in MP-SAN in the high-concentration group were significantly higher than those in the low-concentration group(P&lt;0.01). The addition of verapamil, a P-glycoprotein inhibitor, did not significantly affect the intestinal absorption of DA and Her. However, the absorption of both DA and Her in MP-SAN was significantly increased by the addition of indomethacin(P&lt;0.05),suggesting that DA and Her may be substrates for multidrug resistance-associated protein 2.

The aim of this study was to investigate the effects of solid-state fermented cottonseed meal (FCSM) inclusion levels on the growth performance, serum biochemical parameters and hepatic lipid metabolism in geese from 28 to 70 d of age. A total of 288 twenty-eight-d-old male geese were randomly divided into 4 treatments with FCSM levels of 0, 5, 15 and 25% including 0, 22.74, 67.33, 111.27 mg FG/kg diet, respectively. Each treatment contained 6 replicates and 12 birds per replicate. Treatments of FCSM inclusions from 0 to 25% had no effect on growth rate and feed intake in geese during d 28 to 70. The F/G ratio was increased (P < 0.05) in geese fed the diet with 25% FCSM compared with birds fed the diet with 0% FCSM. Treatment with 25% FCSM levels had no effect on the contents of TC, TG, HDL-C, LDL-C, but increased (P < 0.05) AST and ALT activities in serum of geese at d 70. Treatment with 25% FCSM increased the contents of FG, HDL-C, TC, C18:2n6, C20:4n6 and PUFA and decreased (P < 0.05) the contents of NEFA, SFA, MUFA in liver compared with treatment of 0% FCSM inclusion. Additionally, treatment with 25% FCSM decreased (P < 0.05) the PPARα, AMPK, and LXR mRNA expression related to lipid deposition, and increased (P < 0.05) PPARγ and ACC mRNA expression related to lipolysis in liver compared with birds fed the diet with 0% FCSM. Overall, treatment with 0 to 15% FCSM (<=67.33 mg FG/kg diet) had no adverse effects on the growth performance and lipid metabolism of geese. However, treatment fed 25% FCSM (111.27 mg FG/kg diet) decreased feed efficiency and promoted hepatic lipid deposition associated with the alteration of related gene expression in geese at 28 to 70 d of age., (Copyright © 2024. Published by Elsevier Inc.)

To elucidate the effect of aromatic side chains on dilational rheological properties of N -acyltaurate amphiphiles at the decane-water interface, the interfacial rheological properties of sodium N -2-(2-naphthoxy)-tetradecanoyltaurinate (12+N-T) and sodium N -2-( p -butylphenoxy)-tetradecanoyltaurinate (12+4B-T) were investigated utilizing the drop shape analysis method. The effects of adsorption time, interfacial pressure, oscillating frequency, and bulk concentration on the interfacial dilational modulus and phase angle were explored. The results show that the 12+4B-T molecule with a longer hydrophobic chain shows a higher ability for reducing the interfacial tension (IFT). In addition, the interfacial films of both 12+N-T and 12+4B-T are dominated by diffusion exchange at high concentrations. The rigidity of molecules controls the diffusion exchange at low concentrations, while the molecular hydrodynamic radius determines the diffusion exchange at high concentrations. Thus, at low concentrations, the stronger intermolecular interaction between 12+4B-T molecules results in higher dilational modulus values than 12+N-T. When approaching the CMC (critical micelle concentration) value, the rapid diffusion exchange of 12+4B-T between the sublayer micelles and the interface causes a significant decrease in the dilational modulus, while the relatively rigid structure of 12+N-T enables a higher dilational modulus than 12+4B-T. What's more, the longer hydrophobic chain allows 12+4B-T molecules to escape from the interface more easily, resulting in a higher phase angle at low concentrations. However, the diffusion exchange of 12+4B-T is slower than that of 12+N-T, which results in lower phase angles for 12+4B-T than 12+N-T at high concentrations. In general, the introduction of a rigid naphthalene ring in the molecular structure gives the interfacial film greater strength at high concentration. The research results in this paper provide a new technique for the strength regulation of interfacial surfactant adsorption films.

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages., Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment., Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth., Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy., 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 Xie, Yao, Li, Zhu, Chen, Cao, Cheng, Chen, Huang, Wang, Wang, Qiao, Ge, Yue, Wei, Liu, Han, Qin and Zhao.)

Lay Abstract: Timely detection is an issue of paramount importance in the care of children with autism spectrum disorder. Whether the delayed autism spectrum disorder diagnosis can be explained by children's clinical presentations and socio-familial status in China is a question to be addressed. We investigated 1235 autism spectrum disorder children from 132 rehabilitation organisations in Shenzhen, China. These children were found to have a mean age of diagnosis of 31.4 ± 12.7 months and a median age of diagnosis of 30.0 months. The majority of these children were able to receive their diagnosis during toddlerhood. However, about one in six were not diagnosed until they entered preschool or later, thus missing the golden window of opportunity for early intervention. The age of diagnosis was likely to be late if the children were older, were less severe and presented with no intellectual impairment. The odds of having a delayed autism spectrum disorder diagnosis were more than 9 times higher among migrant autism spectrum disorder children than among those with local household registrations, thus underscoring the importance of identifying culturally sensitive socio-economic determinants in autism spectrum disorder detection, as these factors are likely to affect the quality of life of many autism spectrum disorder children and their families., 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.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA., (© 2024. The Author(s).)

SEMA4D-modified titanium surfaces can indirectly regulate macrophages through endothelial cells to achieve an anti-inflammatory effect, which is beneficial for healing soft tissues around the gingival abutment. However, the mechanism of surface-induced cellular phenotypic changes in SEMA4D-modified titanium has not yet been elucidated. SEMA4D activates the RhoA signaling pathway in endothelial cells, which coordinates metabolism and cytoskeletal remodeling. This study hypothesized that endothelial cells inoculated on SEMA4D-modified titanium surfaces can direct M2 polarization of macrophages via metabolites. An indirect co-culture model of endothelial cells and macrophages was constructed in vitro, and specific inhibitors were employed. Subsequently, endothelial cell adhesion and migration, metabolic changes, Rho/ROCK1 expression, and inflammatory expression of macrophages were assessed via immunofluorescence microscopy, specific kits, qRT-PCR, and Western blotting. Moreover, an in vivo rat bilateral maxillary implant model was constructed to evaluate the soft tissue healing effect. The in vitro experiments showed that the SEMA4D group had stronger endothelial cell adhesion and migration, increased Rho/ROCK1 expression, and enhanced release of lactate. Additionally, decreased macrophage inflammatory expression was observed. In contrast, the inhibitor group partially suppressed lactate metabolism and motility, whereas increased inflammatory expression. The in vivo analyses indicated that the SEMA4D group had faster and better angiogenic and anti-inflammatory effects, especially in the early stage. In conclusion, via the Rho/ROCK1 signaling pathway, the SEMA4D-modified titanium surface promotes endothelial cell adhesion and migration and lactic acid release, then the paracrine lactic acid promotes the polarization of macrophages to M2, thus obtaining the dual effects of angiogenesis and anti-inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In order to explore the mechanism of rockburst in coal seam with rock parting, a combination of on-site and numerical experiment is used to study the failure and instability process, crack propagation mechanism, and influencing factors. The following four points were addressed: (1) the instability is a process that roadway in coal seam with rock parting go through from stable locking in the initial stress unloading stage to slipping unlocking, and then to spatter ejection in slipping dynamic load disturbance stage. (2) The fracture development caused by unloading excavation of coal seam with rock parting will change from shear crack to tensile crack. In this process, coal-rock contact surface slip and coal-rock fracture are coupled with each other. (3) The greater the mining depth is, the greater the lateral pressure coefficient is, and the higher the rockburst risk is. On the contrary, the lower the risk of rockburst. (4) When choosing the support form of roadway in coal seam with rock parting, the two supporting forms of bolting (cable) and supplementary masonry support should be preferred. The results enrich the theory of the dynamics of surrounding rock fracture in coal mine, further clarify the potential dangers to mining-area roadways and working faces, and provide technical information to ensure the safe and efficient mining of bifurcated coal seam., (© 2024. The Author(s).)

Bridging study in vaccine clinical trials means a series of small-scale additional tests on the basis that the original safety and effectiveness of a vaccine have been confirmed in clinical trials, to prove that the characteristics of safety, immunogenicity and effectiveness of a vaccine are similar or consistent after component, population and immunization procedure change to other types which can extrapolate data from existing clinical trials. Compared with traditional vaccine clinical trials, bridging trials can promote the approval of vaccines to the market, accelerate the expansion of vaccine application, and promote the use of vaccines across regions and populations. In recent years, the application of bridge study design in vaccine clinical research has become more and more common. In order to better guide and promote the application of bridging trial design in the field of vaccine clinical research, we reviewed the design characteristics and application examples of bridging study design in vaccine clinical trials, and systematically elaborated the design ideas, key points and statistical evaluation methods of bridging study.

Objectives: This study evaluated the diagnostic value of artificial intelligence-assistant diagnostic system combined with contrast-enhanced ultrasound in The American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) 4 category thyroid nodules., Methods: Thyroid nodules that were evaluated as ACR TI-RADS 4 by conventional ultrasound were selected, all of which had pathological or fine needle aspiration (FNA) results. All nodules were examined by contrast-enhanced ultrasound (CEUS) and artificial intelligence (AI) analysis. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of AI, CEUS and their combined diagnosis were compared; Analyzed and compared the diagnostic efficiency of AI, CEUS and their combined diagnosis., Results: A total of 148 thyroid nodules were included in 140 patients, including 58 malignant nodules and 89 benign nodules. The sensitivity of combined diagnosis was significantly higher than that of AI or CEUS alone (P < .05). The NPV of AI, CEUS and combined diagnosis were statistically significant (P < .05). There was no significant difference in the diagnostic efficacy between AI and CEUS (P > .05), but there was a significant difference in NPV between AI and combined diagnosis (P < .05). The AUC of the combined diagnosis was 0.859, which was higher than that of AI, CEUS alone., Conclusions: AI has a high diagnostic efficiency, which was helpful for radiologists to make rapid assessment. AI combined CEUS can significantly improve the diagnostic sensitivity and NPV, which was beneficial for the early detection of malignant nodules., (© 2023 American Institute of Ultrasound in Medicine.)

This study aimed to investigate whether the developmental changes in glucose metabolism were associated with insulin signaling in the middle and later stages of goose embryos. Serum and liver were sampled on embryonic day 19, 22, 25, 28, and day of hatchment, with 30 eggs at each sampling time point, and 6 replicates of 5 embryos. The embryonic growth traits, serum glucose, hormone levels, and the hepatic mRNA expressions of target genes related to glucose metabolism and insulin signaling were measured at each time point. Relative body weight, relative liver weight, and relative body length decreased linearly and quadratically from embryonic day 19 to day of hatchment, while relative yolk weight decreased linearly from embryonic day 19 to day of hatchment. Serum glucose, insulin, and free triiodothyronine levels increased linearly with increasing incubation time, while no differences were observed in serum glucagon and free thyroxine levels. The hepatic mRNA expression related to glucose catabolism (hexokinase, phosphofructokinase, and pyruvate kinase) and insulin signaling (insulin receptor, insulin receptor substrate protein, Src homology collagen protein, extracellular signal-regulated kinase, and ribosomal protein S6 kinase, 70 ku) increased quadratically from embryonic day 19 to day of hatchment. The expression of citrate synthase and isocitrate dehydrogenase mRNA decreased linearly and quadratically respectively from embryonic day 19 to day of hatchment. Serum glucose levels were positively related to serum insulin (r = 1.00) and free triiodothyronine (r = 0.90) levels, as well as the hepatic mRNA expression of insulin receptor (r = 1.00), insulin receptor substrate protein (r = 0.64), extracellular signal-regulated kinase (r = 0.81), and ribosomal protein S6 kinase, 70 ku (r = 0.81) related to insulin signaling. In conclusion, glucose catabolism was enhanced and had positive correlations with the insulin signaling in the middle and later stages of geese embryogenesis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Xiao'er Qingre Zhike Oral Solution (XQZS) is a commonly used TCM formula to treat cough in children in China. Its complicated composition renders its chemical analysis and mechanism elucidation difficult. To evaluate the bioactive components and mechanism of XQZS against cough, we used a combination strategy of chemical analysis and network pharmacology. A UHPLC/Q-Orbitrap-MS method was established for the identification and qualitative analysis of components of XQZS, and a total of 33 components were unambiguously identified. Aiming at identifying the components, network pharmacology revealed 107 potential targets related to cough. Using protein-protein interactions analysis, nine core targets were selected. Several cough-related pathways were enriched using the Kyoto Encyclopedia of Genes and Genomes, including neuroactive ligand-receptor interaction, serotonergic synapse and dopaminergic synapse. The herb-compound-target-pathway network indicated that PTGS2 (COX-2) was the core target of XQZS against cough. To demonstrate the inhibition effects of the major components against the key target, a COX-2 inhibitor screening assay was used. Compounds P2, P4, P23 and P49 exhibited promising inhibition effects on COX-2 at 20 μm, with inhibitory rates of 55.80-69.87%. In conclusion, this study demonstrates that XQZS may alleviate cough via the inhibition of PTGS2 (COX-2) and the regulation of the serotonergic synapse pathway. The chemical analysis and network pharmacology integrated evaluation provided an efficient strategy for discovering the key pharmacological mechanism of XQZS., (© 2023 John Wiley & Sons Ltd.)

Background: Malnutrition is associated with poor outcomes for geriatric patients in intensive care unit (ICU). It is important to identify patients at risk of malnutrition and provide individual nutrition support. The assessment of malnutrition risk is not easy for these patients due to their cognitive impairment. Geriatric nutrition risk index (GNRI) is a simple and objective scoring tool to evaluate the risk of malnutrition in elderly patients. In this study, we aimed to see whether GNRI score was appropriate to predict clinical outcomes among geriatric patients in the setting of ICU., Materials and Methods: Elderly patients with age ≥ 65 years were extracted from Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Categories based on GNRI were classified as major risk (GNRI <82), moderate risk (GNRI 82 to <92), low risk (GNRI 92 to ≤98), and no risk (GNRI >98). The primary outcome was all-cause hospital mortality. Multivariable Cox proportional hazards regression models and restricted cubic spline were used to investigate associations of GNRI with hospital mortality, respectively. A two-piecewise linear regression model was applied to examine the inflection point of GNRI on hospital mortality. To reduce selection bias, propensity score matching (PSM) was used in a 1:1 ratio., Results: A total of 3,696 geriatric patients were finally included with median age 75 (69, 81) years. The prevalence of major risk was 28.6%. In the fully adjusted model, GNRI categories featured a negative trend with hospital mortality ( p for trend = 0.037). Restricted cubic spline analysis demonstrated an L-shaped relationship between GNRI and hospital mortality before and after matching. The inflection point was 78.7. At the left side of inflection point, GNRI levels were significantly negatively associated with hospital mortality (HR = 0.96, 95% CI: 0.94-0.98; p  < 0.001) and featured no significant relations at the right side. Multiple linear regression also showed that GNRI was negatively associated with length of stay in hospital., Conclusion: The major risk of malnutrition defined by GNRI was able to predict poor prognosis for geriatric patients admitted to ICU., 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 Peng, Zhu, Xing, Li, Gao and Gong.)

The aim of this study is to evaluate the effects of dietary iron sources on growth performance, iron status and activities of Fe-containing enzymes and gene expression related to iron homeostasis in tissues of weaned pigs. A total of 480 piglets at d 28 (Duroc X Landrace) were allotted to four groups as a factorial arrangement of treatments with 30 pigs/pen (male: female = 1:1) and 4 replicate pens/treatment. The treatments for iron in the diets were: control basal diet (Con); Con + 150 mg Fe/kg as inorganic Fe (iFe); Con + 75 mg Fe/kg as inorganic Fe + 75 mg Fe/kg as organic Fe-peptide complex (iFe+oFe) and Con + 150 mg of Fe/kg as organic Fe-peptide complex (oFe). The feeding trial lasted for 36 days. There were no significant differences in final body weight, ADG, ADFI, and G/F as well as blood hemoglobin and MCHC contents between piglets fed the control and iron-supplemented groups ( P > 0.05). The iron supplemented groups exhibited increased iron content in the liver, kidney and spleen as well as the CAT and SDH activities in liver compared to the control group ( P < 0.05), while piglets in oFe group experienced greater Fe accumulation and activities of CAT and SDH in the liver than piglets in the iFe group. Compared with the control group, dietary supplementation of iron increased the NCOA4 mRNA expression and decreased the TfR1 mRNA expression in liver of piglets. The TfR1, NCOA4 and Ferritin mRNA expressions of bone marrow in both iFe and iFe+oFe groups were greater than both in the Con and oFe groups. These results suggest that dietary supplementation of iron does not influence the growth performance and hematological parameters in weaned pigs fed a corn-soybean meal basal diet (75.8 mg/kg) from d 28 to d 70, but increased tissue iron status and activities of Fe-containing enzymes at d 70. The addition of organic Fe-peptide complexes presents greater beneficial effects on enhancing tissue Fe accumulation and Fe-containing enzyme activities, which may be involved in different gene expression patterns related to iron intake and transport in tissues of weaned pigs., Competing Interests: JY, JL, Y-HJ, and R-QH were employed by the Guangdong Guangken Animal Husbandry Group Co., Ltd. The remaining 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 Huang, Yang, Xie, Li, Jian, Yang and Zhu.)

Purpose: To explore the value of virtual surgery and 3D printing model combined with guide plate in treatment of mandibular condylar neck fracture., Methods: Seven patients with mandibular condylar neck fracture were scanned by CT for original data. The data were exported in DICOM format. A three-dimensional model was reconstructed using software, the fracture was reduced by virtual surgery, and the 3D model was printed by a 3D printer. A prebent titanium plate was used to fabricate the guide plate, which was used for reduction and fixation of the fracture block during surgery., Results: All the postoperative incisions revealed no signs of infection, the wounds were hidden and beautiful. The implanted titanium plates were highly compatible with the reduced fracture segments. The patients were followed up for 6 months after surgery, the condylar fracture healed well and there was no obvious displacement. The patient developed no mandibular deviation with a stable occlusion, and no occlusal pain was reported. No obvious temporomandibular joint disorder was present., Conclusions: Virtual surgery and 3D printing model combined with guide plate can ensure an accurate reduction of condylar neck fracture and simplify the operation process, which can be used as an accurate, efficient and predictable auxiliary method.

Background: The certification of immunogenicity consistency at different production scales is indispensable for the quality control of vaccines., Research Design and Methods: A randomized, double-blind immunobridging trial in healthy adults aged 18-59 was divided into Scale A (50 L and 800 L) and Scale B (50 L and 500 L) based on vaccine manufacturing scales. Eligible participants in Scale A were randomly assigned to receive the single-dose recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV) of different scales at a 1:1 ratio, as was Scale B. The primary endpoint was the geometric mean titer (GMT) of anti-live SARS-CoV-2-specific neutralizing antibodies (NAb) 28 days post-vaccination., Results: 1,012 participants were enrolled, with 253 (25%) per group. The post-vaccination GMTs of NAb were 10.72 (95% CI: 9.43, 12.19) and 13.23 (11.64, 15.03) in Scale A 50 L and 800 L, respectively; 11.64 (10.12, 13.39) and 12.09 (10.48, 13.95) in Scale B 50 L and 500 L, respectively. GMT ratios in Scale A and B have a 95% CI of 0.67-1.5. Most adverse reactions were mild or moderate. 17 of 18 participants reported non-vaccination-related serious adverse reactions., Conclusions: The Ad5-nCoV in the scale-up production of 500 L and 800 L showed consistent immunogenicity with the original 50 L production scale, respectively.

Pheromone-binding proteins (PBPs) play important roles in perception of insect sex pheromones, functioning to recognize and transport pheromone components onto the olfactory receptors of the odorant sensing neurons. Orthaga achatina, a serious pest of camphor trees, uses a mixture of three Type I (Z11-16:OAc, Z11-16:OH and Z11-16:Ald) and one Type II (Z3,Z6,Z9,Z12,Z15-23:H) sex pheromone components in its sex communication, in which Z11-16:OAc is the major component and others are minor components. In this study, we for the first time demonstrated that the three PBPs differentiated in recognition among pheromone components in a moth using mixed-type sex pheromones. First, tissue expression study showed that all three PBPs of O. achatina were expressed only in antennae and highly male-biased, suggesting their involvement in perception of the sex pheromones. Second, the three PBPs were expressed in Escherichia coli and the binding affinities of PBPs to four sex pheromone components and some pheromone analogs were determined by the fluorescence competition binding assays. The results showed that OachPBP1 bound all four sex pheromone components with high binding affinity, while OachPBP2 had high or moderate binding affinity only to three Type I components, and OachPBP3 had high binding affinity only to three minor pheromone components. Furthermore, key amino acid residues that bind to sex pheromone components were identified in three PBPs by 3-D structure modeling and ligand molecular docking, predicting the interactions between PBPs and pheromone components. Our study provides a fundamental insight into the olfactory mechanism in moths that use mixed-type sex pheromones., (Copyright © 2022. Published by Elsevier Inc.)

Environmental protection and sustainability have been a serious challenge due to the excess amount of waste plastic, and the inefficient methods of its disposal. This study aims at exploring the feasibility of using plastic material in asphalt concrete followed by the design and evaluation of modified asphalt mix. Four different types of asphalt mixtures were made by mixing mineral aggregates with plastic aggregates of different shapes and sizes. The conventional dense-graded asphalt concrete incorporating mineral aggregates was selected as control material, whereas the other three types of asphalt mixtures were produced by substituting 3D-printed plastic aggregates for mineral aggregates. Marshall characteristics were utilized to evaluate the volumetric and mechanical properties of the asphalt mixtures. Test results show that the asphalt mixture containing solid plastic aggregate appears to have a 14.3% reduction in bulk density, thereby potentially reducing the haul costs. Due to the angular shape of the aggregate, the stability for the asphalt mixture containing the 3D-printed aggregate is 1.95 times higher than that for the asphalt mixture incorporating all mineral aggregates. The addition of the plastic printed aggregate enhances the strain capacity to achieve failure of the asphalt mixture. However, caution should be taken when incorporating the hollow or fine printed aggregates into the asphalt mixture due to their variation of volumetric properties., Competing Interests: No competing financial interests exist., (Copyright 2022, Mary Ann Liebert, Inc., publishers.)

Dynamic electric field frequency actuated helical and spiral structures enable a plethora of attributes for advanced photonics and engineering in the contemporary era. Nevertheless, leveraging the frequency responsiveness of adaptive devices and systems within a broad dynamic range and maintaining restrained high-frequency induced heating remain challenging. Herein, we establish a frequency-actuated heliconical soft architecture that is quite distinct from that of common frequency-responsive soft materials. We achieve reversible modulation of the photonic bandgap in a wide spectral range by delicately coupling the frequency-dependent thermal effect, field-induced dielectric torque and elastic equilibrium. Furthermore, an information encoder prototype without the aid of complicated algorithm design is established to analogize an information encoding and decoding process with a more convenient and less costly way. A technique for taming and tailoring the distribution of the pitch length is exploited and embodied in a prototype of a spatially controlled soft photonic cavity and laser emission. This work demonstrates a distinct frequency responsiveness in a heliconical soft system, which may not merely inspire the interest in field-assisted bottom-up molecular engineering of soft matter but also facilitate the practicality of adaptive photonics., (© 2022. The Author(s).)

Background/aims: Gastrointestinal (GI) dysmotility in acute pancreatitis (AP) aggravates inflammation and results in severe complications. This study aimed to explore effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) on abdominal pain, GI dysmotility, and inflammation in AP patients., Methods: Forty-two AP patients were blindly randomized to receive TEA (n = 21) at acupoints PC6 and ST36 or Sham-TEA (n = 21) at sham points for 2 days. Symptom scores, gastric slow waves, autonomic functions (assessed by spectral analysis of heart rate variability), circulatory levels of motilin, ghrelin, and TNF-α were measured before and after the treatment. Sixteen healthy controls (HCs) were also included without treatment for the assessment of gastric slow waves and biochemistry., Key Results: Compared with Sham-TEA, TEA decreased abdominal pain score (2.57 ± 1.78 vs. 1.33 ± 1.02, p < 0.05), bloating score (5.19 ± 1.21 vs. 0.76 ± 0.99, p < 0.001), the first defecation time (65.79 ± 19.51 h vs. 51.38 ± 17.19 h, p < 0.05); TEA, but not Sham-TEA, improved the percentage of normal gastric slow waves by 41.6% (p < 0.05), reduced AP severity score (5.52 ± 2.04 vs. 3.90 ± 1.90, p < 0.05) and serum TNF-α (7.59 ± 4.80 pg/ml vs. 4.68 ± 1.85 pg/ml, p < 0.05), and upregulated plasma ghrelin (0.85 ± 0.96 ng/ml vs. 2.00 ± 1.71 ng/ml, p = 0.001) but not motilin (33.08 ± 22.65 pg/ml vs. 24.12 ± 13.95 pg/ml, p > 0.05); TEA decreased sympathetic activity by 15.0% and increased vagal activity by 18.3% (both p < 0.05)., Conclusions & Inferences: TEA at PC6 and ST36 administrated at early stage of AP reduces abdominal pain, improves GI motility, and inhibits inflammatory cytokine, TNF-α, probably mediated via the autonomic and ghrelin mechanisms., (© 2021 John Wiley & Sons Ltd.)

Background: Type 2 diabetes mellitus causes left ventricular (LV) remodeling and increases the risk of aortic regurgitation (AR), which causes further heart damage. This study aimed to investigate whether AR aggravates LV deformation dysfunction and to identify independent factors affecting the global peak strain (PS) of LV remodeling in patients with type 2 diabetes mellitus (T2DM) who presented with AR and those without T2DM., Methods: In total, 215 patients with T2DM and 83 age- and sex-matched healthy controls who underwent cardiac magnetic resonance examination were included. Based on the echocardiogram findings, T2DM patients with AR were divided into three groups (mild AR [n = 28], moderate AR [n = 21], and severe AR [n = 17]). LV function and global strain parameters were compared, and multivariate analysis was performed to identify the independent indicators of LV PS., Results: The T2DM patients with AR had a lower LV global PS, peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR) in three directions than those without AR and non-T2DM controls. Patients without AR had a lower PS (radial and longitudinal) and PDSR in three directions and higher PSSR (radial and longitudinal) than healthy controls. Further, regurgitation degree was an independent factor of LV global radial, circumferential, and longitudinal PS., Conclusion: AR may aggravate LV stiffness in patients with T2DM, resulting in lower LV strain and function. Regurgitation degree and sex were independently correlated with LV global PS in patients with T2DM and AR., (© 2022. The Author(s).)

Zinc (Zn) deposition in egg yolk is essential for the rapid growth and complete development of the avian embryo. Thus, it is crucial to obtain maximal Zn mobilization at an appropriate time during development in favor of the survival of avian embryos. The aim of this study was to study the developmental change of Zn mobilization and gene expression related to key Zn transport proteins between the yolk sac membrane and embryonic liver from the incubation d 17 (E17) to d 32 (E32) during duck embryonic developing. The weights of duck embryo, embryo without yolk sac, and embryonic liver increased as well as the yolk sac weight decreased linearly (P < 0.0001) when incubation day increased. The Zn concentration in the yolk sac did not change from E17 to E29 and only declined significantly from E29 to E32 of duck embryos, while hepatic Zn level decreased linearly as with the increased incubation time (P < 0.01). When the incubation day increased, the decreased Zn amount in the yolk sac and the increased Zn amount in the embryonic liver were observed (P < 0.0001). The calculated transfer-out rate of Zn in the yolk sac and transfer-in rate of Zn in livers were both increased from E23-26 to E29-32 (P < 0.01). Among E17, E23 and E29, the solute carrier family 39 member (ZIP) of ZIP10, ZIP13, and ZIP14 genes mRNA expressions were increased in yolk sac membrane but were decreased in the embryonic liver, while metallothionein 1 mRNA expression was increased both in the yolk sac membrane and liver (P < 0.05). In conclusion, yolk sac membrane and embryonic liver tissues displayed the similar developmental patterns of Zn mobilization and metallothionein 1 mRNA expression from E17 to E32 during duck embryonic developing. The appropriate time of the maximal rate of Zn mobilization were observed between E29 and E32 of duck embryo, associated with the significant changes of gene expression related to some key Zn transport proteins on E29 in yolk sac membrane and liver tissues., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alcoholic fatty liver disease (AFLD) is the first stage of the alcoholic liver disease course. Yin-Chen-Hao-Tang (YCHT) has a good clinical effect on the treatment of AFLD, but its molecular mechanism has not been elucidated. In this study, we tried to explore the molecular mechanism of YCHT in improving hepatocyte steatosis in AFLD mice through network pharmacology and RNA sequencing (RNA-Seq) transcriptomics., Methods: Network pharmacological methods were used to analyze the potential therapeutic signaling pathways and targets of YCHT on AFLD. Then, the AFLD mice model was induced and YCHT was administered concurrently. Liver injury was measured by serum alanine aminotransferase (ALT) activity and liver tissue H&E staining, and liver steatosis was determined by serum triglyceride (TG) level and liver tissue Oil Red staining. The molecular mechanism of YCHT on prevention and treatment of mice AFLD was investigated according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differential expression genes data obtained by liver tissue RNA-Seq. Finally, ethanol-induced AFLD AML12 hepatocyte model was established, YCHT with or without PPAR α agonist pemafibrate or PPAR γ inhibitor GW9662 was administered, Nile Red fluorescent staining was used to evaluate steatosis levels in AML12 hepatocytes, and qRT-PCR was used to detect PPAR α and PPAR γ gene expression., Results: The results of network pharmacology analysis showed that YCHT may exert its pharmacological effect on AFLD through 312 potential targets which are involved in many signaling pathways including the PPAR signaling pathway. AFLD mice experiments results showed that YCHT markedly decreased mice serum ALT activity and serum TG levels. YCHT also significantly improved alcohol-induced hepatic injury and steatosis in mice livers. Furthermore, KEGG pathway enrichment results of RNA-Seq showed that the PPAR signaling pathway should be the most relevant pathway of YCHT in the prevention and treatment of AFLD. AFLD hepatocyte model experiment results showed that YCHT could remarkably reduce hepatocyte steatosis through reducing PPAR γ expression and increasing PPAR α expression., Conclusions: Our study discovered that PPAR γ and PPAR α are the key targets and the PPAR signaling pathway is the main signaling pathway for YCHT to prevent and treat AFLD., Competing Interests: All authors declare that they have no conflicts of interest., (Copyright © 2021 Yi-Wei Zhu et al.)

Universities are important sources of knowledge and key members of the regional innovation system. The key problem in Chinese universities is the low efficiency of the scientific and technological (S&T) transformation, which limits the promotion of regional innovation and economic development. This article proposes the three-stage efficiency analytical framework, which regards it as a complex and interactive process. Avoiding the problem of considering the input and output of university S&T transformation as a "black box" and neglecting the links among different transformation stages. The super efficiency network SBM model is applied to the heterogeneous region of the Yangtze River Economic Belt. Empirical research proves that university S&T transformation has not been effectively improved and the scientific resources invested in universities have not been efficiently utilized in recent years. Generally, Despite the correlation between regional economy and transformation efficiency, the exclusive increase in resources is not enough. Regional openness and the quality of research talents are key factors for the application of technological innovation and technology marketization. Universities should not only pursue the number of research outputs but pay more attention to high-quality knowledge production to overcome difficulties in research achievements transformation., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study was performed to evaluate the occlusion of monetite paste on dentine tubule and provide a new potential method for treating dentine hypersensitivity., Methods: Calcium oxide, strontium chloride, and polyethylene glycol phosphate were mixed in a certain proportion and ground in a planetary ball mill. The reaction was carried out by adjusting the pH to obtain monetite and hydroxyapatite paste. The morphological characteristics of the paste were observed through scanning electron microscope (SEM). The structure and composition were analyzed through X-ray diffraction (XRD) and Fourier transform infrared spectrometer (FTIR). The extracted third molar was selected to undergo demineralization to establish the in vitro study model of dentin hypersensitivity. The samples were randomly divided into four groups: blank control group (treated with distilled water), casein peptide phosphate-amorphic calcium phosphate (CPP-ACP) group, monetite paste group, and hydroxyapatite paste group. Each group was used to scrub the dentin surface with the corresponding materials for 7 days. The morphological characteristics of the dentin surface and section were observed through SEM, the microhardness of the dentin before and after mineralization was analyzed with a microhardness tester, and the composition of the deposits on the surface of the mineralized samples was examined through XRD., Results: XRD and FTIR showed that the composition of the paste was mainly monetite, and the composition of hydroxyapatite paste was mainly composed of hydroxyapatite. SEM revealed that the size of the crystal particles of the synthesized paste was tens to hundreds of nanometers. Monetite and hydroxyapatite paste could produce a thicker mineralization layer on the dentin surface, and the mineralization of the dentin tubules of monetite was deeper than that of hydroxyapatite paste. The microhardness of the monetite paste group was significantly less than those of the hydroxyapatite paste groups ( P <0.05)., Conclusions: Monetite paste could effectively block the exposed dentin tubules and be used for treating dentin hypersensitivity.

In western societies, the prevalence of type 2 diabetes (T2D) is related to the hygiene hypothesis, which implies that reduced exposure to infectious factors results in a loss of the immune stimulation necessary to form the immune system during development. In fact, it has been reported that parasites, such as Schistosoma, can improve or prevent the development of T2D, which may be related to the activity of immune cells, including regulatory T cells (Tregs). Hence, Schistosoma, Tregs, and T2D share a close relationship. Schistosoma infection and the molecules released can lead to an increase in Tregs, which play an important role in the suppression of T2D. In this review, we provide an overview of the role of Tregs in the response to Schistosoma infection and the protective mechanism of Schistosoma-related molecular products against T2D., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Medical waste (MW) has exploded since the COVID-19 pandemic and aroused great concern to MW disposal. Meanwhile, the energy recovery for MW disposal is necessary due to high heat value of MW. Harmless disposal of MW with economically and environmentally sustainable technologies along with higher energy recovery is urgently required, and their energy recovery efficiencies and environmental impacts reduction due to energy recovery are key issues. In this study, five MW disposal technologies, i.e. rotary kiln incineration, pyrolysis incineration, plasma melting, steam sterilization and microwave sterilization, were evaluated and compared via energy recovery analysis (ERA), life cycle assessment (LCA), and life cycle costing (LCC) methods. Furthermore, three MW incineration technologies with further energy recovery and two sterilization followed by co-incineration technologies were analyzed to explore their improvement potential of energy recovery and environment benefits via scenario analysis. ERA results reveal that the energy recovery efficiencies of "steam and microwave sterilization + incineration" are the highest (≥83.4%), while that of the plasma melting is the lowest (19.2%). LCA results show that "microwave sterilization + landfill" outperforms others while the plasma melting exhibits the worst, electricity is the most significant contributor to the environmental impacts of five technologies. Scenario analysis shows that the overall environmental impact of all technologies reduced by at least 45% after further heat utilization. LCC results demonstrate that pyrolysis incineration delivers the lowest economic cost, while plasma melting is the highest. Co-incineration of sterilized MW and municipal solid waste could be recommended., 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 © 2021 Elsevier B.V. All rights reserved.)

The Schistosoma japonicum fatty acid-binding protein (FABP) is used in the cell membrane to absorb and transport fatty acids, which cannot be resynthesized by the organism and combined with hydrophobic ligands. Among the 5 stages of the worm life cycle examined, FABP messenger ribonucleic acid (mRNA) expression was highest in male adult worms, followed by the liver-stage schistosome, and was the lowest in the lung-stage schistosome. The fabp gene-coding region was cloned and expressed to obtain recombinant S. japonicum FABP (rSjFABP) with a molecular weight of approximately 18 kDa. Mice were then immunized against rSjFABP to prepare anti-FABP serum. Using immunohistochemical techniques, FABP protein was found to localize to the eggshell, parenchyma, and digestive tract. Double-stranded RNA-mediated knockdown of FABP mRNA by RNA interference decreased the number of transcripts by >70%. Moreover, the egg production rate decreased, whereas the abnormal egg ratio was significantly increased in the FABP-silenced group compared with the negative control group (P < 0.05). These results demonstrate that FABP localizes in adults and in various stages. FABP contributes to the egg-laying capacity of adults, which may be related to the reproductive function of S. japonicum., (© American Society of Parasitologists 2021.)

Nuciferine (NF) has received extensive attention due to its medicinal value in the treatment of metabolic diseases, such as obesity; however, to date, the effects of NF on obesity-related intestinal permeability, autophagy and the gut microbiota have not been investigated. Herein, C57BL/6J mice were fed either a chow or a high-fat diet (HFD) with or without NF for 8 weeks. The results showed that NF supplement reduced weight gain, fat accumulation and intestinal permeability in the HFD mice accompanied by improved autophagy. Subsequently, an in vitro experiment was performed using Caco-2 and HT-29 cells, which showed that NF supplement not only promoted the formation of autophagosomes and autophagolysosomes, but also alleviated LPS-increased intestinal permeability. Importantly, NF supplement protected from LPS-induced paracellular permeability impairment after the administration of autophagy-related gene (Atg) 5 small-interfering RNA (siRNA). These results demonstrate that NF exerts beneficial effects on the intestinal permeability by improving autophagy. Furthermore, we also found that NF supplement lowered the abundance of Butyricimonas and increased the abundance of Akkermansia, an anti-obesity bacterium. Thus, overall, we demonstrated that NF supplement confers reduced intestinal permeability by improving autophagy and alters the composition of the gut microbiota in HFD-fed mice, thereby producing an anti-obesity effect.

Background: Apigenin, as a natural flavonoid, has low intrinsic toxicity and has potential pharmacological effects against hepatocellular carcinoma (HCC). However, the molecular mechanisms involving microRNAs (miRNAs) and their target genes regulated by apigenin in the treatment of HCC have not been addressed., Objective: In this study, the molecular mechanisms of apigenin involved in the prevention and treatment of HCC were explored in vivo and in vitro using miRNA transcriptomic sequencing to determine the basis for the clinical applications of apigenin in the treatment of HCC., Methods: The effects of apigenin on the proliferation, cell cycle progression, apoptosis, and invasion of human hepatoma cell line Huh7 and Hep3B were studied in vitro , and the effects on the tumorigenicity of Huh7 cells were assessed in vivo . Then, a differential expression analysis of miRNAs regulated by apigenin in Huh7 cells was performed using next-generation RNA sequencing and further validated by qRT-PCR. The potential genes targeted by the differentially expressed miRNAs were identified using a curated miRTarBase miRNA database and their molecular functions were predicted using Gene Ontology and KEGG signaling pathway analysis., Results: Compared with the control treatment group, apigenin significantly inhibited Huh7 cell proliferation, cell cycle, colony formation, and cell invasion in a concentration-dependent manner. Moreover, apigenin reduced tumor growth, promoted tumor cell necrosis, reduced the expression of Ki67, and increased the expression of Bax and Bcl-2 in the xenograft tumors of Huh7 cells. Bioinformatics analysis of the miRNA transcriptome showed that hsa-miR-24, hsa-miR-6769b-3p, hsa-miR-6836-3p, hsa-miR-199a-3p, hsa-miR-663a, hsa-miR-4739, hsa-miR-6892-3p, hsa-miR-7107-5p, hsa-miR-1273g-3p, hsa-miR-1343, and hsa-miR-6089 were the most significantly up-regulated miRNAs, and their key gene targets were MAPK1, PIK3CD, HRAS, CCND1, CDKN1A, E2F2, etc. The core regulatory pathways of the up-regulated miRNAs were associated with the hepatocellular carcinoma pathway. The down-regulated miRNAs were hsa-miR-181a-5p and hsa-miR-148a-3p, and the key target genes were MAPK1, HRAS, STAT3, FOS, BCL2, SMAD2, PPP3CA, IFNG, MET, and VAV2, with the core regulatory pathways identified as proteoglycans in cancer pathway., Conclusion: Apigenin can inhibit the growth of HCC cells, which may be mediated by up-regulation or down-regulation of miRNA molecules and their related target genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Yang, Feng, Zhu, Qiu, Hu and Zhang.)

Background and Aim: Huashi Baidu Decoction (HSBD) is a novel complex prescription which has positive effects on severe COVID-19. This study was aimed to discover key Chinese materia medica, main active compounds, hub therapeutic target proteins and core signal pathways in the potential therapeutic mechanism of HSBD on severe COVID-19 through integrating network pharmacological methods., Experimental Procedure: TCMSP, TCMID and STITCH databases were used to screen out active compounds and target proteins of HSBD. GeneCards database was used to screen out disease genes of severe COVID-19. The potential therapeutic targets of HSBD on severe COVID-19 were used to construct protein-protein interaction network through STRING database and the hub target proteins were discovered. Next, GO and KEGG enrichment analysis were carried out to discover core signal pathways. Finally, the network diagram of "Chinese materia medica-active compounds-therapeutic target proteins" was built, then key Chinese materia medica and main active compounds were selected., Results and Conclusion: HSBD might treat severe COVID-19 through 45 potential target genes, among them, there were 13 hub target genes: RELA, TNF, IL6, IL1B, MAPK14, TP53, CXCL8, MAPK3, MAPK1, IL4, MAPK8, CASP8, STAT1. Meanswhile, GO&#95;BiologicalProcess and KEGG signaling pathways analysis results showed that the core signal pathways were inflammation and immune regulation pathways. Finally, 4 key Chinese materia medica and 11 main active compounds were discovered in the HSBD. In conclusion, the therapeutic mechanism of HSBD on severe COVID-19 might involve its pharmacological effects of anti-inflammation and immune regulation via acting on 45 disease-related proteins of severe COVID-19., Taxonomy Classification by Evise: Viral Pneumonia, COVID-19, Acute Respiratory Distress Syndrome, Septic Shock, Chinese Herbal Medicine., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)