MOVER tests for non-inferiority of the difference between two binary-outcome treatments in the matched-pairs design.

A non-inferiority trial is usually conducted to investigate whether a new drug/treatment is no worse than a reference drug/treatment by a small, pre-specified, non-inferiority margin. This study aimed to assess the non-inferiority of the difference between two binary-outcome treatments in a matched-pairs design based on the method of variance of estimates recovery (MOVER). The processes for estimating the confidence interval of a single proportion included in the MOVER are the Wilson score interval, Agresti - Coull interval, Jeffreys interval, modified Jeffreys interval, score method with continuity correction, and arcsin interval. The performance of the six MOVER tests, the fiducial test, and the restricted maximum likelihood estimation test were evaluated by comparing their type I error rates and power at different pre-assigned levels and with varying combinations of parameters. The evaluation results showed that the modified Jeffreys MOVER test can be a competitive alternative to the other recommended tests. It can control type I errors well, and its power is not inferior to other methods. The proposed tests were illustrated with three real-world examples.

Association of child maltreatment and school bullying among Chinese adolescents: the mediating role of peer relationships.

BACKGROUND: School bullying, a serious problem for the physical and mental health of adolescents, is presently a significant issue in China. It is essential to recognize and comprehend potential risk factors and establish efficient preventive strategies. The purpose of this study was to examine the association between childhood maltreatment and school bullying in adolescents and to assess the mediating role of peer relationships. METHODS: Between March and April 2024, a cross-sectional survey was conducted among 2119 adolescents aged between 12 and 18 years in Guangdong Province, China. Self-report questionnaires were employed to collect data on childhood maltreatment, school bullying, and peer relationships. Subgroup analyses and mediating effects modeling were employed to analyze the data. RESULTS: The results indicated that adolescents who had experienced maltreatment were more at risk of bullying victimization (OR: 2.92, 95% CI: 2.34-3.64, P < 0.001), bullying perpetration (OR: 2.84, 95% CI: 1.99-4.05, P < 0.001), and bully-victimization (OR: 2.93, 95% CI: 1.95-4.41, P < 0.001), compared to adolescents who have not. Sexual abuse showed the most significant connection with all forms of bullying. The mediating effect of peer relationships was found to mediate the association between child maltreatment and bullying behaviour. The results indicated that worse peer relationships may exacerbate the adverse effects of maltreatment experiences and increase the risk of adolescents becoming bullies, either perpetrators or victims of bullying. CONCLUSIONS: Child maltreatment has been identified as one of the most significant influences on bullying behaviour in adolescents. The quality of peer relationships has been demonstrated to play an important role in preventing and reducing the occurrence of bullying. The results underscore the crucial role of early intervention in cases of child maltreatment and the fostering of positive peer relationships in schools.

Posterior reversible encephalopathy syndrome triggered by FLOT (5-fluorouracil, oxaliplatin, docetaxel, and calcium levofolinate) chemotherapy and thrombocytopenia (docetaxel and cisplatin) chemotherapy.

INTRODUCTION: Posterior reversible encephalopathy syndrome is a clinical and imaging syndrome characterized by endothelial dysfunction, blood-brain barrier disruption, and vasogenic edema. The common clinical symptoms of posterior reversible encephalopathy syndrome include headache, altered consciousness, visual disturbances, and seizures, among which headache and seizures are the most common. The classic imaging patterns usually reveal vasogenic edema. CASE REPORT: We describe the case of a middle-aged woman with gastric cancer. She was under treatment by fluorouracil, leucovorin, oxaliplatin, and docetaxel regimen and thrombocytopenia regimen after tumor progression, but developed unconsciousness, irritability, and headache shortly after initiation of treatment. Her magnetic resonance imaging in our hospital shows abnormal signals in bilateral frontal parietal occipital lobes with hyperintensities on T2-weighted magnetic resonance imaging and fluid-attenuated inversion recovery imaging, accompanied by the increased value of apparent diffusion coefficient. And T1-weighted images illustrate hypointense foci, with increased diffusion-weighted imaging signals. MANAGEMENT AND OUTCOME: After admission, she was treated to control blood pressure, reduce brain edema, expand blood vessels, improve consciousness, and symptomatic support treatment. 3 days after the onset of the disease, her headache symptoms and state of consciousness gradually improved, and her blood pressure can be controlled at about 130/80 mmHg. DISCUSSION: This is the first report that posterior reversible encephalopathy syndrome is caused by a thrombocytopenia regimen, and our case highlights the pathogenic role of a thrombocytopenia regimen in posterior reversible encephalopathy syndrome. However, the association between the thrombocytopenia regimen and previous fluorouracil, leucovorin, oxaliplatin, and docetaxel regimens needs further study.

Research progress in the early diagnosis of Parkinson's disease.

Parkinson's disease is the second major neurodegenerative disease with increasing incidence and population in the world year by year. The pathogenesis of Parkinson's disease is still not completely clear, and the identification of Parkinson's disease prodromal manifestations and accurate diagnosis is still facing great challenges. This review summarizes the interaction of environmental toxicants, mitochondrial dysfunction, α-synuclein, gut microbiome dysbiosis, neuroinflammation, and other pathophysiological factors in Parkinson's disease. It also discusses the prodromal manifestations of Parkinson's disease, such as olfactory dysfunction, sleep dysfunction and other non-motor symptoms, the current diagnostic challenges, and the application status of emerging neuroimaging technologies such as magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission tomography (SPECT).

Combined inoculation with dark septate endophytes and arbuscular mycorrhizal fungi: synergistic or competitive growth effects on maize?

BACKGROUND: Effects on maize were assessed of dual inoculation with arbuscular mycorrhizal fungi (AMF) and dark septate endophytes (DSE) isolated from other plant species. METHODS: Suspensions of DSE isolated from Stipa krylovii were prepared at different densities (2, 4, and 8 × 105 CFU mL- 1) and inoculated separately (AMF or DSE) or together (AMF + DSE), to explore their effects on maize growth. RESULTS: Inoculation with AMF or medium and high densities of DSE and combined inoculation (AMF + DSE) increased plant above-ground growth and altered root morphology. Differences in plant growth were attributable to differences in DSE density, with negative DSE inoculation responsiveness at low density. AMF promoted plant above-ground growth more than DSE and the high density of DSE promoted root development more than AMF. Combined inoculation might lead to synergistic growth effects on maize at low density of DSE and competitive effects at medium and high DSE densities. CONCLUSIONS: AMF and DSE co-colonized maize roots and they had positive effects on the host plants depending on DSE density. These findings indicate the optimum maize growth-promoting combination of AMF and DSE density and provide a foundation for further exploration of potentially synergistic mechanisms between AMF and DSE in physiological and ecological effects on host plants.

A Type VI Secretion System Facilitates Fitness, Homeostasis, and Competitive Advantages for Environmental Adaptability and Efficient Nicotine Biodegradation.

Gram-negative bacteria employ secretion systems to translocate proteinaceous effectors from the cytoplasm to the extracellular milieu, thus interacting with the surrounding environment or microniche. It is known that bacteria can benefit from the type VI secretion system (T6SS) by transporting ions to combat reactive oxygen species (ROS). Here, we report that T6SS activities conferred tolerance to nicotine-induced oxidative stress in Pseudomonas sp. strain JY-Q, a highly active nicotine degradation strain isolated from tobacco waste extract. AA098_13375 was identified to encode a dual-functional effector with antimicrobial and anti-ROS activities. Wild-type strain JY-Q grew better than the AA098_13375 deletion mutant in nicotine-containing medium by antagonizing increased intracellular ROS levels. It was, therefore, tentatively designated TseN (type VI secretion system effector for nicotine tolerance), homologs of which were observed to be broadly ubiquitous in Pseudomonas species. TseN was identified as a Tse6-like bacteriostatic toxin via monitoring intracellular NAD+ TseN presented potential antagonism against ROS to fine tune the heavy traffic of nicotine metabolism in strain JY-Q. It is feasible that the dynamic tuning of NAD+ driven by TseN could satisfy demands from nicotine degradation with less cytotoxicity. In this scenario, T6SS involves a fascinating accommodation cascade that prompts constitutive biotransformation of N-heterocyclic aromatics by improving bacterial robustness/growth. In summary, the T6SS in JY-Q mediated resistance to oxidative stress and promoted bacterial fitness via a contact-independent growth competitive advantage, in addition to the well-studied T6SS-dependent antimicrobial activities.IMPORTANCE Mixtures of various pollutants and the coexistence of numerous species of organisms are usually found in adverse environments. Concerning biodegradation of nitrogen-heterocyclic contaminants, the scientific community has commonly focused on screening functional enzymes that transform pollutants into intermediates of attenuated toxicity or for primary metabolism. Here, we identified dual roles of the T6SS effector TseN in Pseudomonas sp. strain JY-Q, which is capable of degrading nicotine. The T6SS in strain JY-Q is able to deliver TseN to kill competitors and provide a growth advantage by a contact-independent pattern. TseN could monitor the intracellular NAD+ level by its hydrolase activity, causing cytotoxicity in competitive rivals but metabolic homeostasis on JY-Q. Moreover, JY-Q could be protected from TseN toxicity by the immunity protein TsiN. In conclusion, we found that TseN with cytotoxicity to bacterial competitors facilitated the nicotine tolerance of JY-Q. We therefore reveal a working model between T6SS and nicotine metabolism. This finding indicates that multiple diversified weapons have been evolved by bacteria for their growth and robustness.

Additional Role of Nicotinic Acid Hydroxylase for the Transformation of 3-Succinoyl-Pyridine by Pseudomonas sp. Strain JY-Q.

Nicotine and nicotinic acid (NA) are both considered to be representatives of N-heterocyclic aromatic compounds, and their degradation pathways have been revealed in Pseudomonas species. However, the cooccurrence of these two pathways has only been observed in Pseudomonas sp. strain JY-Q. The nicotine pyrrolidine catabolism pathway of strain JY-Q consists of the functional modules Nic1, Spm, and Nic2. The module enzyme, 3-succinoylpyridine monooxygenase (Spm), catalyzes transformation of 3-succinoyl-pyridine (SP) to 6-hydroxy-3-succinoyl-pyridine (HSP). There exist two homologous but not identical Spm enzymes (namely, Spm1 and Spm2) in JY-Q. However, when spm1 and spm2 were both in-frame deleted, the mutant still grew well in basic salt medium (BSM) supplemented with nicotine as the sole carbon/nitrogen nutrition, suggesting that there exists an alternative pathway responsible for SP catabolism in JY-Q. NicAB, an enzyme accounting for NA hydroxylation, contains reorganized domains similar to those of Spm. When the JY-Q_nicAB gene (nicAB in strain JY-Q) was introduced into another Pseudomonas strain, one that is unable to degrade NA, the resultant recombinant strain exhibited the ability to transform SP to HSP, but without the ability to metabolize NA. Here, we conclude that NicAB in strain JY-Q exhibits an additional role in SP transformation. The other genes in the NA cluster, NicXDFE (Nic2 homolog), then also exhibit a role in subsequent HSP metabolism for energy yield. This finding also suggests that the cooccurrence of nicotine and NA degradation genes in strain JY-Q represents an advantage for JY-Q, making it more effective and flexible for the degradation of nicotine.IMPORTANCE 3-Succinoyl-pyridine (SP) and 6-hydroxy-3-succinoyl-pyridine (HSP) are both valuable chemical precursors to produce insecticides and hypotensive agents. SP and HSP could be renewable through the nicotine microbial degradation pathway, in which 3-succinoylpyridine monooxygenases (Spm) account for transforming SP into HSP in Pseudomonas sp. strain JY-Q. However, when two homologous Spm genes (spm1 and spm2) were knocked out, the mutant retained the ability to degrade nicotine. Thus, in addition to Spm, JY-Q should have an alternative pathway for SP conversion. In this research, we showed that JY-Q_NicAB was responsible for this alternative SP conversion. Both of the primary functions for nicotinic acid dehydrogenation and the additional function for SP metabolism were detected in a recombinant strain harboring JY-Q_NicAB. As a result, both nicotinic acid and nicotine degradation pathways in JY-Q contribute to its remarkable nicotine tolerance and nicotine degradation availability. These findings also provide one more metabolic engineering strategy for accumulation for value-added intermediates.

Pharmacokinetic study of three different formulations of l-tetrahydropalmatine in brain tissues of rats.

l-Tetrahydropalmatine (l-THP), an active alkaloid compound isolated from Rhizoma Corydalis-yanhusuo, has been reported to possess biological activity for treating cocaine use. To enhance both oral bioavailability and brain penetration, three formulations of l-THP suspension, mixture of l-THP-puerarin and self-microemulsifying drug delivery systems (SMEDDS) were prepared. A sensitive and reliable ultra-high-performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of l-THP and its active metabolite l-isocorypalmine (l-ICP) in rat brain. Diazepam was used as the internal standard. The chromatographic separation was achieved on a Bonshell ASB C18 column at 30°C using acetonitrile-aqueous formic acid as mobile phase in gradient mode. The linearity was validated over the concentration ranges of 4.00-2,500 ng/ml for l-THP and 0.400-500 ng/ml for l-ICP. Full method validation was within the acceptance limits. The method was successfully used to determine the pharmacokinetics of two analytes following oral administration of these three formulations to rats. A significant difference was observed in the main pharmacokinetic parameters between SMEDDS and the suspension, and a 3.25- and 2.97-fold increase in the relative bioavailability of l-THP and l-ICP, respectively, was observed with the SMEDDS compared with the suspension formulation. It was concluded that SMEDDS enhanced the absorption of l-THP and l-ICP and delayed their release in brain.

MxB impedes the NUP358-mediated HIV-1 pre-integration complex nuclear import and viral replication cooperatively with CPSF6.

BACKGROUND: The human myxovirus resistance 2 (Mx2/MxB) protein was originally found to regulate cytoplasmic-nuclear transport but was recently reported to restrict HIV-1 replication by binding to HIV-1 capsid (CA), preventing uncoating, the nuclear import of pre-integration complex (PIC) and viral DNA integration. This work explores the mechanisms of MxB-mediated HIV-1 inhibition. RESULTS: We demonstrated that MxB represses NUP358-mediated PIC nuclear import and HIV-1 replication. Moreover, MxB's effects on PIC nuclear import and HIV-1 replication depend critically on cofactor cleavage and polyadenylation specificity factor subunit 6 (CPSF6). MxB binds nucleoporin NUP358, blocks NUP358-CA interaction, thereby impeding the nuclear import of HIV-1 PIC with CPSF6 binding to PIC. More intriguingly, CPSF6's role in nuclear import depends on MxB, being a facilitator of HIV-1 nuclear import on its own, but becoming an inhibitor when MxB is present. CONCLUSIONS: Our work establishes that MxB impedes the NUP358-mediated HIV-1 nuclear import and viral replication cooperatively with CPSF6.

Analysis of heart injury laboratory parameters in 273 COVID-19 patients in one hospital in Wuhan, China.

An outbreak of severe acute respiratory syndrome novel coronavirus (SARS-CoV-2) epidemic spreads rapidly worldwide. SARS-CoV-2 infection caused mildly to seriously and fatally respiratory, enteric, cardiovascular, and neurological diseases. In this study, we detected and analyzed the main laboratory indicators related to heart injury, creatine kinase isoenzyme-MB (CK-MB), myohemoglobin (MYO), cardiac troponin I (ultra-TnI), and N-terminal pro-brain natriuretic peptide (NT-proBNP), in 273 patients with COVID-19 and investigated the correlation between heart injury and severity of the disease. It was found that higher concentration in venous blood of CK-MB, MYO, ultra-TnI, and NT-proBNP were associated with the severity and case fatality rate of COVID-19. Careful monitoring of the myocardiac enzyme profiles is of great importance in reducing the complications and mortality in patients with COVID-19.

IFN-λs inhibit Hantaan virus infection through the JAK-STAT pathway and expression of Mx2 protein.

Hantaan virus (HTNV), member of the newly defined Hantaviridae family, within the order Bunyavirales, can cause a hemorrhagic fever with renal syndrome with high fatality rates in humans. However, no specific antiviral agents are currently available for HTNV infection approved by the US Food and Drug Administration. Although interferon lambdas (IFN-λs) have been shown to induce an antiviral state against HTNV, the molecular mechanisms remain to be determined. In this study, we found that IFN-λs exerted its anti-HTNV effect by activating Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway-mediated antiviral immunity in A549 cells. Simultaneously, IFN-λs downregulated suppressor of cytokine signaling proteins, which are the known negative feedback regulators of the JAK-STAT signaling pathway. Additionally, we demonstrated the role of IFN-λs-induced myxovirus resistance 2 (Mx2, also known as MxB) protein as a potential inhibitor for HTNV infection. These findings indicate that IFN-λs play an important role in cellular defenses against HTNV infection at an early stage and that human Mx2 may represent a potential therapeutic target for HTNV infection.

CRISPR/Cas9-mediated deletion of miR-146a enhances antiviral response in HIV-1 infected cells.

The human immunodeficiency virus type 1 (HIV-1) causes persistent infection in human and induces miR-146a expression in infected cells. miR-146a represses the innate immune response by inhibiting the expression of TRAF6 and IRAK1 genes, thus negatively controls the NF-κB-related cytokines and interferon stimulated genes. Here we reported that lentiviral CRISPR/Cas9 system was highly efficient in introducing mutations in the precursor miR-146a genomic sequences, resulting in a loss of miR-146a expression and function. miR-146a ablation led to increasing cytokines production in LPS-stimulated A549 cells. Moreover, miR-146a knockout in HIV-1 infected MT2 cells markedly increased the expression of cytokines and HIV-1 restriction factors and reversed T cell exhaustion markers expression, thus influencing HIV-1 replication. Our study indicates that lentiviral CRISPR/Cas9-mediated gene editing is an effective approach to abrogate miR-146a expression, which consequently inhibits HIV-1 replication as well as proviral reactivation by enhancing the expression of cytokines and HIV-1 restriction factors.

Metabolite profiling of l-isocorypalmine in rat urine, plasma, and feces after oral administration using high performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry.

l-Isocorypalmine, an active alkaloid compound isolated from Rhizoma Corydalis yanhusuo, has been reported to possess biological activity for treating cocaine use disorder. A high-performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry method was established for identification of the metabolites of l-isocorypalmine in urine, plasma and feces samples of rats after a single intragastric gavage of l-isocorypalmine at a dose of 15 mg/kg. As a result, a total of 21 metabolites (six phase І metabolites and fifteen phase II metabolites) were detected and tentatively identified by mass spectrometry and fragment ions from tandem mass spectrometry spectra. All metabolites were present in the urine samples, nine metabolites were found in the plasma samples and three metabolites were found in the feces samples. Results indicated that metabolic pathways of l-isocorypalmine included oxidation, dehydrogenation, demethylation, sulfate conjugation, and glucuronide conjugation. In addition, glucuronidation was the major metabolic reaction. Results of this investigation could provide significant experimental basis for efficacy, safety and action mechanism of l-isocorypalmine, which will be advantageous to new drug development for treating cocaine addiction.

The expression and role of lncRNA AX800134 in hepatitis B virus-related hepatocellular carcinoma.

Chronic infection with hepatitis B virus (HBV) is one of most important risk factors for the development of hepatocellular carcinoma (HCC). Several long non-coding RNAs (lncRNAs) have been shown to be involved in the etiology of HBV-related HCC. AX800134 is one recently identified lncRNA associated with HCC. In this study, we validated the upregulated expression of AX800134 in HBV-positive HCC compared with HBV-negative HCC. Furthermore, we found that HBV X protein (HBx) directly triggered AX800134 expression in human hepatoma HepG2 cells. Pro-inflammatory cytokine TNFα also induced AX800134 upregulation in HBx-expressing HepG2 cells, which could be reversed by reactive oxygen species (ROS) scavenger pyrrolidine dithiocarbamate (PDTC). Additionally, silencing AX800134 with siRNA interference remarkably inhibited the growth and invasion of HBx-expressing HepG2 cells. AX800134 antagonism also enhanced spontaneous apoptosis of HepG2 cells under serum deprivation condition. Therefore, our results indicate that highly expressed AX800134 acts as an oncogenic factor in HCC, and its upregulation is related with the viral product HBx and chronic inflammation.

Compatibility effects of herb pair Phellodendri chinensis cortex and Anemarrhenae rhizoma on benign prostatic hyperplasia using targeted metabolomics.

Phellodendri chinensis cortex (P. C. cortex) and Anemarrhenae rhizoma (A. rhizoma) herb pair is a core component of traditional Chinese medicines used to treat inflammation and benign prostatic hyperplasia (BPH). The present study was designed to profile the arachidonic acid (AA) metabolomic characteristics in rat plasma and prostate after being treated with P. C. cortex and A. rhizoma as well as their combination. Plasma and prostate samples from sham group, BPH model group, herb pair group and two single herb groups were collected on days 7, 14, 21 and 28. Then, a systemic metabolomic analysis based on UFLC-MS/MS was employed to quantify AA and its cyclooxygenase and lipoxygenase pathway metabolites (15-HETE, 12-HETE, 5-HETE, AA, PGI2 , PGF2α , 8-HETE, PGD2 , PGE2 and LTB4 ). The results demonstrated that BPH led a significant increase of 10 biomarkers in plasma and tissue (p < 0.05). The clusters of herb pair group and single herb groups showed a tendency to return to the initial space, and the AA and its metabolites from those groups were differently downregulated to a healthier level, with the combination of single herbs most obvious. The present study demonstrated that P. C. cortex-A. rhizoma herb pair might produce synergistic or complementary compatibility effects on suppressing inflammatory processes occurring in BPH.

Values of procalcitonin and C-reactive proteins in the diagnosis and treatment of chronic obstructive pulmonary disease having concomitant bacterial infection.

OBJECTIVE: To observe the changes in the levels of C-reactive protein (CRP) and procalcitonin (PCT) in serum of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and to compare with the values of CRP in combination with PCT in the diagnosis and treatment of infective exacerbation of COPD. METHODS: One hundred and sixty-four patients who developed acute exacerbation of COPD and admitted to the Binzhou People's Hospital from March 2014 to December 2015 were selected. They were divided into an infection group (N=98) and a non-infection group (N=66) according to bacterial culture results of sputum and lung computer tomography (CT) examination results. Moreover, 50 healthy people were selected as a normal control group. The levels of PCT and CRP of the three groups were determined respectively; patients in the infection group and non-infection group were determined again after administration of antibacterial drugs for a period of time. The results were all recorded. RESULTS: The levels of PCT and CRP of the infection group were significantly higher than those of the non-infection group and the normal control group before treatment, and the difference had statistical significance (P<0.05). The levels of PCT and CRP were (1.97±0.13) µg/L and (7.34±2.66) mg/L respectively in the infection group after treatment, which was much lower than the levels before treatment (P<0.05). The level of PCT of the infection group was remarkably higher than that of the non-infection group after treatment (P<0.05), but the difference of CRP level between the infection group and non-infection group had no statistical significance (P>0.05). The specificity and sensitivity of diagnosing COPD in combination with bacterial infection with PCT or CRP were lower than those of PCT in combination with CRP. CONCLUSION: Levels of CRP in combination with PCT is a reliable index for determining the existence of bacterial infection, which is of great clinical guidance significance to the treatment and prognosis assessment of AECOPD patients.

Expression of HIV-encoded microRNA-TAR and its inhibitory effect on viral replication in human primary macrophages.

A number of virus-encoded microRNAs have been shown to play important roles in virus replication and virus-host interactions, although the expression and function of miR-TAR-3p derived from the human immunodeficiency virus type 1 (HIV-1) TAR element remain controversial. In this study, miR-TAR-3p was detected in human peripheral blood monocyte-derived macrophages (MDMs) infected by HIV-1. Overexpression of miR-TAR-3p impaired viral replication, while inhibition of miR-TAR-3p enhanced it. Additionally, miR-TAR-3p repressed viral transcription and replication by targeting the TAR element in the HIV-1 5'-LTR in a sequence-specific manner. These results confirm the presence of miR-TAR-3p in HIV-1-infected MDMs and suggest that its function might be used as a mechanism to modulate HIV-1 replication through the expression of a negative regulatory factor.

Association between Body Mass Index and Externalizing and Internalizing Symptoms among Chinese Adolescents: Mediating Role of Traditional Bullying and Cyberbullying Victimization.

BACKGROUND: Externalizing problems, internalizing problems, and obesity are among the greatest challenges to adolescent health. However, the moderating and mediating mechanisms that underlie this association remain predominantly unexplored. OBJECTIVES: In this study, we examined the association between body mass index (BMI) and externalizing and internalizing scores in adolescents, tested whether traditional bullying and cyberbullying mediated the association, and explored the moderated role of sex. METHODS: The data came from 1486 adolescents from grade 7, 8, and 10 living in Shantou, China. Information on BMI, traditional bullying, and cyberbullying victimization was obtained through a self-administered questionnaire. The students' externalizing and internalizing scores were evaluated using the Strengths and Difficulties Questionnaire (SDQ). Furthermore, we built two parallel mediation models with sex as a moderating variable. RESULTS: Compared to their peers with normal weight, adolescents with increased BMI reported higher externalizing and internalizing scores. Traditional bullying and cyberbullying were both significant mediators in the two relationships. Sex moderated the pathway from BMI to cyberbullying. But sex did not moderate the relationship between BMI and traditional bullying. CONCLUSIONS: The results highlight that it is imperative for educators to identify students who are subjected to weight-based bullying and provide them with recommendations for effective coping strategies. Meanwhile, both victims of traditional bullying and those affected by cyberbullying should be the focus of prevention and intervention efforts when developing a strategy to improve levels of internalizing and externalizing symptoms among adolescents with increased BMI.

Temporal modulation of inflammation and chondrogenesis through dendritic nanoparticle-mediated therapy with diclofenac surface modification and strontium ion encapsulation.

Cartilage tissue engineering holds great promise for efficient cartilage regeneration. However, early inflammatory reactions to seed cells and/or scaffolds impede this process. Consequently, managing inflammation is of paramount importance. Moreover, due to the body's restricted chondrogenic capacity, inducing cartilage regeneration becomes imperative. Thus, a controlled platform is essential to establish an anti-inflammatory microenvironment before initiating the cartilage regeneration process. In this study, we utilized fifth-generation polyamidoamine dendrimers (G5) as a vehicle for drugs to create composite nanoparticles known as G5-Dic/Sr. These nanoparticles were generated by surface modification with diclofenac (Dic), known for its potent anti-inflammatory effects, and encapsulating strontium (Sr), which effectively induces chondrogenesis, within the core. Our findings indicated that the G5-Dic/Sr nanoparticle exhibited selective Dic release during the initial 9 days and gradual Sr release from days 3 to 15. Subsequently, these nanoparticles were incorporated into a gelatin methacryloyl (GelMA) hydrogel, resulting in GelMA@G5-Dic/Sr. In vitro assessments demonstrated GelMA@G5-Dic/Sr's biocompatibility with bone marrow stem cells (BMSCs). The enclosed nanoparticles effectively mitigated inflammation in lipopolysaccharide-induced RAW264.7 macrophages and significantly augmented chondrogenesis in BMSCs cocultures. Implanting BMSCs-loaded GelMA@G5-Dic/Sr hydrogels in immunocompetent rabbits for 2 and 6 weeks revealed diminished inflammation and enhanced cartilage formation compared to GelMA, GelMA@G5, GelMA@G5-Dic, and GelMA@G5/Sr hydrogels. Collectively, this study introduces an innovative strategy to advance cartilage regeneration by temporally modulating inflammation and chondrogenesis in immunocompetent animals. Through the development of a platform addressing the temporal modulation of inflammation and the limited chondrogenic capacity, we offer valuable insights to the field of cartilage tissue engineering.

Structures and Biological Activities of Secondary Metabolites from Xylaria spp.

The fungus genus Xylaria is an important source of drug discoveries in scientific fields and in the pharmaceutical industry due to its potential to produce a variety of structured novel and bioactive secondary metabolites. This review prioritizes the structures of the secondary metabolites of Xylaria spp. from 1994 to January 2024 and their relevant biological activities. A total of 445 new compounds, including terpenoids, nitrogen-containing compounds, polyketides, lactones, and other classes, are presented in this review. Remarkably, among these compounds, 177 compounds show various biological activities, including cytotoxic, antimicrobial, anti-inflammatory, antifungal, immunosuppressive, and enzyme-inhibitory activities. This paper will guide further investigations into the structures of novel and potent active natural products derived from Xylaria and their potential contributions to the future development of new natural drug products in the agricultural and medicinal fields.