Role of liver sinusoidal endothelial cell in metabolic dysfunction-associated fatty liver disease.

Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells that represent the interface between blood cells on one side and hepatocytes on the other side. LSECs not only form a barrier within the hepatic sinus, but also play important physiological functions such as regulating hepatic vascular pressure, anti-inflammatory and anti-fibrotic. Pathologically, pathogenic factors can induce LSECs capillarization, that is, loss of fenestra and dysfunction, which are conducive to early steatosis, lay the foundation for the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), and accelerate metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. The unique localization, phenotype, and function of LSECs make them potential candidates for reducing liver injury, inflammation, and preventing or reversing fibrosis in the future.

Cellular Uptake Mechanism of Nucleic Acid Nanocapsules and Their DNA-Surfactant Building Blocks.

Nucleic acid nanocapsules (NANs) are enzyme-responsive DNA-functionalized micelles built for the controlled release of DNA-surfactant conjugates (DSCs) that present sequences with demonstrated therapeutic potential. Here, we investigate the mechanisms by which DSCs gain access to intracellular space in vitro and determine the effects of serum on the overall uptake and internalization mechanism of NANs. Using pharmacological inhibitors to selectively block certain pathways, we show, through confocal visualization of cellular distribution and flow cytometry quantification of total cellular association, that scavenger receptor-mediated, caveolae-dependent endocytosis is the major cellular uptake pathway of NANs in the presence and absence of serum. Furthermore, as NANs can be triggered to release DSCs by external stimuli such as enzymes, we sought to examine the uptake profile of particles degraded by enzymes prior to cell-based assays. We found that while scavenger receptor-mediated, caveolae-dependent endocytosis is still at play, energy-independent pathways as well as clathrin-mediated endocytosis are also involved. Overall, this study has helped to elucidate early steps in the cytosolic delivery and therapeutic activity of DSCs packaged into a micellular NAN platform while shedding light on the way in which DNA functionalized nanomaterials in general can be trafficked into cells both as nanostructures and as molecular entities. Importantly, our study also shows that the NAN design in particular is able to stabilize nucleic acids when delivered in the presence of serum, a critical step for effective therapeutic nucleic acid delivery.

Beneficial Effects of Angiotensin II Receptor Blockers on Mortality in Patients with COVID-19: A Retrospective Study from 2019 to 2020 in China.

BACKGROUND: The COVID-19 pandemic has become a serious global public health problem. Although the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 blockers (ARBs) has been recommended in patients with COVID-19 and cardiovascular diseases (CVDs), according to the results of some small-sample retrospective analyses, there remains a lack of sufficient evidence to validate their efficacy. This multicenter retrospective study investigated whether ACEI/ARB administration was beneficial in patients with COVID-19 and CVDs. METHODS: A total of 11,231 patients with confirmed COVID-19 and CVDs, from 138 hospitals in Hubei Province, were included in this multicenter retrospective study. We compared the clinical characteristics and outcomes between the ARB and non-ARB groups and analyzed the risk factors for in-hospital death using univariate and multivariate Cox regression analyses and Kaplan-Meier curves. RESULTS: In the multivariate Cox regression model, after adjusting for age, gender, comorbidities, and in-hospital medications, ARB use was associated with lower all-cause mortality (adjusted HR, 0.53; 95% CI, 0.38-0.73; P < 0.001). After propensity score-matched analysis, the adjusted HR for the use of ARB associated with all-cause mortality was 0.62 (95% CI, 0.40-0.88; P = 0.02). Further subgroup analyses found that the adjusted HRs for the use of ARB associated with all-cause mortality were 0.52 (95% CI, 0.30-0.89; P = 0.016), 0.37 (95% CI, 0.21-0.64; P < 0.001), 0.42 (95% CI, 0.28-0.64; P < 0.001), and 0.55 (95% CI, 0.37-0.84; P = 0.005) in patients with heart failure, diabetes, and hypercholesterolemia, and severe COVID-19, respectively. CONCLUSIONS: ARB administration was significantly associated with a lower risk of all-cause mortality in patients with COVID-19 and CVDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05615792. https://www. CLINICALTRIALS: gov/ct2/show/NCT05615792.

Regulatory perspective for quality evaluation of lipid nanoparticle-based mRNA vaccines in China.

In recent years, urgent unmet medical needs due to the COVID-19 pandemic have accelerated the application of mRNA technology in vaccine development, leading to some of the first approvals of mRNA vaccines in human history by regulatory agencies around the world. For market authorization, comprehensive chemistry, manufacturing and control (CMC) information is required to assure the safety and quality consistency of mRNA vaccines. Evaluating mRNA vaccines for new virus variants poses a challenge for regulators, given the rapid optimization and development based on prior platform knowledge to accelerate the development process, which is traditionally limited for biological products. Here we summarize the current regulatory considerations of CMC evaluation on mRNA vaccines based on the scientific knowledge available, which will be updated with the advance of mRNA biology and pharmaceutical science.

Wuhan 3 years after the outbreak of the pandemic-cardiological insights and perspectives.

In November 2019, Wuhan, a city in Central China, became the center of an outbreak of pneumonia of unknown cause, which was later named "coronavirus disease 2019" (COVID-19). COVID-19 is caused by the novel severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection. The emergence of novel SARS-CoV­2 strains and mutations exerted a serious global public health threat. Although various vaccines have been developed, specific anti-SARS-CoV­2 drugs are limited. As cardiologists, we believe that because SARS-CoV­2 can bind to the angiotensin 2 receptor on the surface of cardiomyocytes, it may also lead to cardiac injury. COVID-19-associated cardiac injury is not rare in clinical practice, and most of these cases are mild, while a few might progress to fulminant myocarditis (FM). Overactivated immune response and inflammatory storm represent the core pathogenesis of COVID-19-associated FM. Early identification and diagnosis of COVID-19-associated FM are critical for its treatment. Recently, Wuhan was hit by the Omicron variant again. We proposed managing COVID-19-associated cardiac injury according to the severity, which has had a significant effect on outcome.

Effects of Age and Sex on Aerobic Fitness, Sprint Performance, and Change of Direction Speed in High School Athletes.

ABSTRACT: Hackett, DA, He, W, Fleeton, JRM, Orr, R, and Sanders, RH. Effects of age and sex on aerobic fitness, sprint performance, and change of direction speed in high school athletes. J Strength Cond Res 37(5): 325-331, 2023-The purpose of this study was to examine the effects of sex and age on aerobic fitness, sprinting performance, and change of direction speed (CODS) in high school athletes, with consideration for maturity. This cross-sectional study involved 2,132 adolescents (1,415 male and 717 female athletes) aged 12.0-15.9 years. Assessment of aerobic fitness using the 20-m multistage fitness test (20MSFT) and 20-m sprint and CODS using the 505 test was performed. For the analysis of data, subjects were separated into 4 age groups: U/13 years, U/14 years, U/15 years, and U/16 years. Estimated age at peak height velocity was a covariate in the data analysis to control for maturity status. Compared with female athletes, male athletes had superior performances at all age groups in 10-m sprint ( p < 0.001, effect size [ES] = >-0.44), 20-m sprint ( p < 0.001, ES = >-0.55), and 505 test ( p < 0.001, ES = >-0.41). Female athletes performed better than male athletes in 20MSFT at U/13 ( p < 0.01, ES = -0.22); however, male athletes had better performances at U/15 ( p < 0.01, ES = 0.27) and U/16 ( p < 0.001, ES = 0.67). At each consecutive age group, male athletes improve their performances in 20MSFT and sprints and at U/14 and U/16 in the 505 test ( p < 0.001, ES > -0.37). Female athletes showed no improvement in the 20MSFT and 505 test between U/13-U/16 but showed improved sprint performance at U/15 compared with U/13 and at U/16 compared with U/14 ( p < 0.05). This study shows that adolescent male athletes perform consistently better than female athletes in running-related field-based tests and display continuous improvements across age groups.

Analysis of the efficacy of a modified posteromedial approach for Klammer III posterior Pilon fractures.

PURPOSE: To analyze the curative effect and technical points of a modified posteromedial approach in the treatment of Klammer III posterior Pilon fracture. METHODS: A retrospective analysis of patients with Klammer III posterior Pilon fractures were conducted in our department from January 2018 to December 2019. Before the surgery, the patients were fully relieved of swelling and pain, and a comprehensive examination was carried out. The posteromedial approach exposed the posterior and medial fracture block of the distal tibia. According to the fracture of external malleolus, it is determined whether to combine a lateral incision and protect tendons and vascular nerves by a retractor, and then perform a fracture reduction and internal fixation. Postoperatively, the patients were treated with analgesia, detumescence, anticoagulation and rehabilitation exercise. The American orthopaedic foot and ankle society (AOFAS) score and visual analogue score were recorded at regular follow-up after surgery. A t-test was used for the comparison of the preoperative and final AOFAS score. RESULTS: There were 7 male and 13 female (n = 20) included in the study, aged 22 to 88 years (average age 54.2 years). The injury mechanisms were falling from a height (n = 7), traffic accident (n = 6), walking injury (n = 2) and heavy injury (n = 5). The postoperative follow-up duration was 12-24 months (mean 16.95 months). The AOFAS score of the 20 patients before and after surgery were compared. The preoperative AOFAS score was 38.90 ± 3.91, and the final AOFAS score was 80.55 ± 4.20, (p < 0.001). The mean final visual analogue scores at rest, active and weight-bearing walking were 0.30, 0.85 and 1.70, respectively. One patient reported poor postoperative wound healing and required a return to hospital for debridement and anti-infection treatment. CONCLUSION: In the treatment of Klammer III posterior Pilon fractures, the modified posteromedial approach can fully expose the fracture block and the collapsed articular surface of the medial malleolus, achieve good reduction and internal fixation with limited injury of the tendon and vascular nerves, and have a better prognosis.

Ghrelin attenuate cerebral microvascular leakage by regulating inflammation and apoptosis potentially via a p38 MAPK-JNK dependent pathway.

Ghrelin is a peptide hormone with strong anti-inflammatory properties. In fact, Ghrelin was reported to improve endothelial dysfunction caused by excessive fat. However, its role in preserving the integrity of brain microvascular, under conditions of lipid dysregulation and inflammation, is not known. The objective of this study is to characterize the role of Ghrelin in the protection of cerebral microvascular integrity, during atherosclerosis, and uncover its underlying molecular mechanism. Our results demonstrated that an atherosclerotic condition, brought on by a high fat diet (HFD), can produce massive increases in serum inflammatory factors, blood lipids, cerebral microvascular leakage, and activation of the p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) (p38 MAPK-JNK) pathway. It also produced significantly damaged pericytes morphology, resulting in pericyte decrease. Ghrelin treatment, on the other hand, protected against cerebral microvascular leakage and pericytes damage. Ghrelin effectively downregulated the expression of pro-inflammatory cytokines, and it also suppressed the p38 MAPK-JNK signaling pathway. Additionally, in isolated mouse cerebral microvascular pericytes, ox-LDL lead to increased apoptosis and secretion of inflammatory factors, along with an elevation in phosphorylated p38 MAPK-JNK proteins. Alternately, Ghrelin administration markedly lowered expression of inflammatory factors, suppressed the p38 MAPK-JNK signaling path, and halted cell apoptosis. However, pretreatment of Hesperetin, a p38 MAPK-JNK agonist, abrogated the Ghrelin-mediated suppression of inflammation and apoptosis in pericytes. Taken together, these results suggest that Ghrelin restored cerebral microvascular integrity and reduced vascular leakage in atherosclerosis mice, in part, by its regulation of inflammatory and apoptotic signaling pathways in pericytes.

Effects of age and sex on field-based measures of muscle strength and power of the upper and lower body in adolescents.

Field-based tests including the medicine ball chest throw (MBCT) and vertical jump are used to assess muscle performance. To date no study has compared performances of these field-based tests in adolescents across a range of ages. The aim of this study was to examine the effects of age and sex on MBCT and countermovement jump (CMJ) performance in adolescents.This cross-sectional study involved 2192 adolescents (1477 males and 715 females) aged between 12 and 17 years. Trials of the MBCT and CMJ were performed with CMJ peak power estimated. Males had significantly greater MBCT distance, CMJ height and CMJ peak power at each consecutive age group separated by 1 year (p < 0.001). Females generally showed significantly greater performances across a larger age range of at least 2 years for MBCT (p ≤ 0.004) and CMJ peak power (p ≤ 0.018). Males had greater performances than females for MBCT distance, CMJ height, and CMJ peak power from 13 years and above (p < 0.001). Sex differences widened with increasing age for all tests from ~5-8% at 12 years progressing to 24-29% at 16-17 years. This study shows the effects of age and sex is similar for both the MBCT and CMJ tests in adolescents.

Information technology solutions, challenges, and suggestions for tackling the COVID-19 pandemic.

Various technology innovations and applications have been developed to fight the coronavirus pandemic. The pandemic also has implications for the design, development, and use of technologies. There is an urgent need for a greater understanding of what roles information systems and technology researchers can play in this global pandemic. This paper examines emerging technologies used to mitigate the threats of COVID-19 and relevant challenges related to technology design, development, and use. It also provides insights and suggestions into how information systems and technology scholars can help fight the COVID-19 pandemic. This paper helps promote future research and technology development to produce better solutions for tackling the COVID-19 pandemic and future pandemics.

Chinese Trauma Surgeon Association for management guidelines of vacuum sealing drainage application in abdominal surgeries-Update and systematic review.

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.

Gene expression profiles of glomerular endothelial cells support their role in the glomerulopathy of diabetic mice.

Endothelial dysfunction promotes the pathogenesis of diabetic nephropathy (DN), which is considered to be an early event in disease progression. However, the molecular changes associated with glomerular endothelial cell (GEC) injury in early DN are not well defined. Most gene expression studies have relied on the indirect assessment of GEC injury from isolated glomeruli or renal cortices. Here, we present transcriptomic analysis of isolated GECs, using streptozotocin-induced diabetic wildtype (STZ-WT) and diabetic eNOS-null (STZ-eNOS-/-) mice as models of mild and advanced DN, respectively. GECs of both models in comparison to their respective nondiabetic controls showed significant alterations in the regulation of apoptosis, oxidative stress, and proliferation. The extent of these changes was greater in STZ-eNOS-/- than in STZ-WT GECs. Additionally, genes in STZ-eNOS-/- GECs indicated further dysregulation in angiogenesis and epigenetic regulation. Moreover, a biphasic change in the number of GECs, characterized by an initial increase and subsequent decrease over time, was observed only in STZ-eNOS-/- mice. This is consistent with an early compensatory angiogenic process followed by increased apoptosis, leading to an overall decrease in GEC survival in DN progression. From the genes altered in angiogenesis in STZ-eNOS-/- GECs, we identified potential candidate genes, Lrg1 and Gpr56, whose function may augment diabetes-induced angiogenesis. Thus, our results support a role for GEC in DN by providing direct evidence for alterations of GEC gene expression and molecular pathways. Candidate genes of specific pathways, such as Lrg1 and Gpr56, can be further explored for potential therapeutic targeting to mitigate the initiation and progression of DN.

A thrombopoietin receptor antagonist is capable of depleting myelofibrosis hematopoietic stem and progenitor cells.

Recently, interactions between thrombopoietin (TPO) and its receptor, the myeloproliferative leukemia (MPL) virus oncogene, have been shown to play a role in the development and progression of myeloproliferative neoplasms including myelofibrosis (MF). These observations have led to the development of strategies to disrupt the association of TPO with its receptor as a means of targeting MF hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). In this report, we show that although both splenic and peripheral blood MF CD34(+) cells expressed lower levels of MPL than normal CD34(+) cells, TPO promoted the proliferation of MF CD34(+) cells and HPCs in a dose-dependent fashion. Furthermore, the treatment of MF but not normal CD34(+) cells with a synthesized MPL antagonist, LCP4, decreased the number of CD34(+)Lin(-) cells and all classes of assayable HPCs (colony-forming unit-megakaryocyte [CFU-MK], CFU-granulocyte/macrophage, burst-forming unit-erythroid/CFU-erythroid, and CFU-granulocyte/erythroid/macrophage/MK) irrespective of their mutational status. In addition, LCP4 treatment resulted in the depletion of the number of MF HPCs that were JAK2V617F(+) Moreover, the degree of human cell chimerism and the proportion of malignant donor cells were significantly reduced in immunodeficient mice transplanted with MF CD34(+) cell grafts treated with LCP4. These effects of LCP4 on MF HSCs/HPCs were associated with inhibition of JAK-STAT activity, leading to the induction of apoptosis. These findings demonstrate that such specific anti-cytokine receptor antagonists represent a new class of drugs that are capable of targeting MF HSCs.

Round Window Niche Drilling with Intratympanic Steroid Is a Salvage Therapy of Sudden Hearing Loss.

OBJECTIVE: To explore the effectiveness and safety of round window niche drilling combined with intratympanic methylprednisolone injection for the salvage treatment of sudden sensorineural hearing loss (SSNHL) and its associated tinnitus after failed primary treatment. METHOD: SSNHL patients who showed a less than 10-dB improvement of pure-tone average after receiving standard systemic treatment and intratympanic steroid injection were enrolled. All included patients were randomly divided into two groups (control and study). Patients in the study group received round window niche drilling combined with daily intratympanic methylprednisolone for 7 times; the control group received only daily intratympanic methylprednisolone for 7 times. One month after treatment, the improvements of PTA, speech discrimination score (SDS), tinnitus and the incidence of adverse events were analyzed. RESULTS: 20 patients (10 for each group) were included in this study. The baseline between two groups showed no statistical significance. Patients in the study group experienced an average hearing improvement of 20.38 dB, SDS 19.3 compared with 2.1 dB and SDS 2.0 in the control group. None (0%) in the control group and 4 patients (40%) showed marked recovery, 5 patients (50%) showed slight improvement of hearing in the study group after 1 month. All patients in the study group showed significant recovery of tinnitus. Both tinnitus handicap inventory and a symptom visual analogue scale between two groups revealed statistical differences (p < 0.001, p = 0.002, respectively). None in the control and study groups experienced vertigo, infection and facial paralysis. CONCLUSION: Round window niche drilling increases the contact area and time of methylprednisolone. It is an effective and safe salvage therapy of idiopathic SSNHL and its induced tinnitus.

Effects of combination of balloon Eustachian tuboplasty with methylprednisolone irrigation on treatment of chronic otitis media with effusion in adults.

PURPOSE: Adult chronic otitis media with effusion (COME) is characterized by Eustachian tube dysfunction and mucosal inflammation, which management has long been a challenge because of high recurrence. This study was to investigate the pathological changes of Eustachian tube mucosa and optimized treatment. MATERIALS AND METHODS: Retrospective study of four groups: I: tympanic paracentesis, II: balloon Eustachian tuboplasty (BET), III: BET plus tympanic paracentesis, IV: BET and tympanic paracentesis with methylprednisolone irrigation. Biopsy of Eustachian tube mucosa was obtained preoperative and 1 month post. Recurrence ratio and Eustachian tube scores (ETS) were used to evaluate the effect of treatments. RESULTS: All patients showed narrowed with edematous and thickened Eustachian tube mucosa. At 1 month post-treatment, BET with methylprednisolone irrigation significantly decreased intraepithelial inflammation and restored the quality of epithelium and cilia. For group II to IV, The recurrence rate was significantly lower in group IV compared with the other two, but only significantly lower in group IV VS group II at 3 months and 6 months, no significant difference at 12 months. The recurrence rate was significantly higher in group I during follow-up. The ETS were improved in group II, III and IV after treatment. At 1 month and 3 months posttreatment, group IV had significant higher ETS compared with other groups (P < 0.05). There was no serious complications occurred. CONCLUSION: Methylprednisolone irrigation could help to recover mucosal function. BET and tympanic paracentesis with methylprednisolone irrigation could be regarded as a good choice for COME in adults, which has less recurrence rate and prompt recovery of ET function.

Comparison of Glomerular and Podocyte mRNA Profiles in Streptozotocin-Induced Diabetes.

Evaluating the mRNA profile of podocytes in the diabetic kidney may indicate genes involved in the pathogenesis of diabetic nephropathy. To determine if the podocyte-specific gene information contained in mRNA profiles of the whole glomerulus of the diabetic kidney accurately reflects gene expression in the isolated podocytes, we crossed Nos3(-/-) IRG mice with podocin-rtTA and TetON-Cre mice for enhanced green fluorescent protein labeling of podocytes before diabetic injury. Diabetes was induced by streptozotocin, and mRNA profiles of isolated glomeruli and sorted podocytes from diabetic and control mice were examined 10 weeks later. Expression of podocyte-specific markers in glomeruli was downregulated in diabetic mice compared with controls. However, expression of these markers was not altered in sorted podocytes from diabetic mice. When mRNA levels of glomeruli were corrected for podocyte number per glomerulus, the differences in podocyte marker expression disappeared. Analysis of the differentially expressed genes in diabetic mice also revealed distinct upregulated pathways in the glomeruli (mitochondrial function, oxidative stress) and in podocytes (actin organization). In conclusion, our data suggest reduced expression of podocyte markers in glomeruli is a secondary effect of reduced podocyte number, thus podocyte-specific gene expression detected in the whole glomerulus may not represent that in podocytes in the diabetic kidney.

Influence of the Ring Size on the Binding Ability of FTO Investigated by Fluorescence Spectroscopy.

The fat mass and obesity associated protein (FTO) is a potential target for anti-obesity medicines. In this paper, we have synthesized two potential inhibitors for FTO, three-member-ring compound (W 3 ) and four-member-ring compound (W 4 ). The interactions of fat mass and obesity-associated (FTO) protein with W 3 (or W 4 ) have been studied by spectral method. Results show the intrinsic fluorescence is quenched by the W 3 (or W 4 ). The thermodynamics parameters indicate hydrophobic interaction play a major role in the interactions. The results of synchronous fluorescence spectra demonstrate that the microenvironments of Trp residue of FTO are disturbed by W 3 and W 4 . Results showed that W 3 are stronger quenchers and bind to FTO with the higher affinity than W 4 . The influence of molecular structure on the binding aspects has been investigated.

Anti-hepatitis B virus activity of α-DDB-FNCG, a novel nucleoside-biphenyldicarboxylate compound in vitro and in vivo.

A novel codrug, α-DDB-FNCG, was synthesized through coupling of α-biphenyl dimethyl dicarboxylate (α-DDB) and the nucleoside analogue FNCG, via an ester bond. The anti-HBV activity and hepatoprotective effects of this compound were investigated both in vitro and in vivo. In HBV-transfected HepG2.2.15 cell line, the secretion of HBsAg and HBeAg as well as the levels of extracellular and intracellular viral DNA were determined by ELISA and real-time fluorescent quantitative Polymerase Chain Reaction (FQ-PCR), respectively. In DHBV-infected ducks, the viral DNA levels in serum and liver were determined by FQ-PCR. In addition, the levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in both serum and liver were also examined. The improvement of ducks' livers was evaluated by histopathological analysis. It has been demonstrated that α-DDB-FNCG could suppress the levels of HBV antigens and viral DNA in a time- and dose-dependent manner in the HepG2.2.15 cell line. Furthermore, this codrug could also significantly inhibit the viral DNA replication and reduce the ALT and AST levels in both serum and liver of DHBV-infected ducks, with improved hepatocellular architecture in drug-treated ducks. In short, these results suggest that α-DDB-FNCG could be a promising candidate for further development of new anti-HBV agents with hepatoprotective effects.

From growth and fixed creative mindsets to creative thinking: an investigation of the mediating role of creativity motivation.

Studies documenting and seeking to understand the mindset effect have yielded mixed and inconclusive findings. The present study sought to address the research question pertaining to the mindset effect on creative thinking and its underlying mechanism from the perspectives of social cognitive theory and mindset theory, which postulate a motivational mechanism underlying the mindset-creativity link. Specifically, this study aimed to examine the mediating role of creativity motivation in the effects of growth and fixed creative mindsets on creative thinking. A convenience sample of 948 college students from three universities in Hong Kong participated in the study. Creative mindset, creativity motivation, and creative thinking were assessed using the Chinese version of the Creative Mindset Scale, the Creativity Motivation Scale, and the Test for Creative Thinking-Drawing Production (TCT-DP), respectively. Lending support to the perspectives of social cognitive and mindset theories, the results of mediation analyses conducted using Preacher and Hayes's bootstrapping approach indicated that creativity motivation had partial mediating effects on the positive and negative roles of growth and fixed mindsets, respectively, in creative thinking. Enriching the research on the motivation mechanism underlying the impacts of creative mindsets on creative thinking, the results further illustrated that creativity motivation has a stronger mediating effect on the impact of growth creative mindset on creative thinking than on that of fixed creative mindset. The possible theoretical and educational implications of the findings of this research are discussed.

Effects of age and playing position on field-based physical fitness measures in adolescent female soccer players.

BACKGROUND: While numerous studies have explored age and playing position effects on fitness levels in male adolescent soccer players, research on female players in this context is lacking. The purpose of this study was to examine the effects of age and playing position on field-based physical fitness measures in adolescent female soccer players, with consideration for maturity. METHODS: This cross-sectional study involved 284 females aged 12.0-15.9 years. Participants performed the 20-m multi-stage fitness test (20MSFT) to assess estimated maximum oxygen uptake (VO2max), 10-m and 20-m sprints, 505 Test to evaluate change of direction speed (CODS), the medicine ball chest throw (MBCT) and countermovement vertical jump (CMVJ) to assess muscle power. For data analysis, participants were separated into age groups (12, 13, 14, and 15 years), and playing position (forward, midfielder, defender, and goalkeeper). Age at peak height velocity was considered a covariate to account for maturity status. RESULTS: Players aged 14 years demonstrated faster CODS compared to 15 years old (P=0.014), while superior MBCT performance was noted at both ages compared to younger ages (P<0.001). Goalkeepers exhibited lower VO2max than midfielders and defenders (P<0.05). Defenders and goalkeepers exhibited greater hip circumference and body mass compared to midfielders (P≤0.01), along with a larger waist circumference for defenders compared to midfielders (P=0.003). Age and position interactions were absent. When analyses were run without controlling for maturity, all results were the same except for CODS where no age effect was found. CONCLUSIONS: This study suggests that upper body power, and flexibility may be impacted by age and playing position in adolescent female soccer players, regardless of maturity status. The CODS appears to be influenced by age only when controlling for maturity.