Six new polyphenolic metabolites isolated from the Suillus granulatus and their cytotoxicity against HepG2 cells.

Edible mushrooms are an important source of nutraceuticals and for the discovery of bioactive metabolites as pharmaceuticals. In this work, six new polyphenolic metabolites suillusol A-D (1-4), suillusinoic acid (5), ethyl suillusinoate (6), were isolated from the Suillus granulatus. The structures of new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy, nuclear magnetic resonance data, and single-crystal X-ray diffraction analysis. As far as we know, compound 1 represents an unprecedented type of natural product and compound 3 represents a new type of polyphenol fungal pigment, which may be biosynthetically related to thelephoric acid. The cytotoxicity against HepG2 cells of the new compounds were also evaluated. Compound 2 demonstrate significant inhibitory activity against HepG2 cells with IC50 values of 10.85 µM, surpassing that of positive control cisplatin. Moreover, compound 1 and 3 also exhibited moderate cytotoxic activity with their IC50 values measured at 35.60 and 32.62 µM, respectively. Our results indicate that S. granulatus is a rich source of chemical constituents that may provide new lead compounds for the development of anticancer agents.

Chemical Compounds, Bioactivities, and Potential Applications of the Mushroom Species of Genus Suillus (Agaricomycetes): A Review.

The genus Suillus, also known as "Song mo," falls under the order Boletales and consists of various higher fungi. It establishes mycorrhizae primarily with pine trees and has a good taste and medicinal values. Herein, we reviewed the chemical compounds present in the genus Suillus, including polysaccharides, steroids, phenols, polyprenyl phenol derivatives, fatty acids, organic acids, and amino acids, and their reported bioactivities and potential applications. This review aims to promote the utilization of the resources belonging to the genus Suillus and serves as a theoretical basis for their future studies and clinical applications.

Longitudinal Relation between Harsh Punishment and Psychoticism among Chinese Early Adolescents: Disentangling between­ and within­Family Effects.

This longitudinal study examined bidirectional relations between parental harsh punishment and psychoticism at the between­ and within­family levels in Chinese adolescents. There were 3,307 Chinese youth (43.6% girls, Mage = 11.30 years, SD = 0.24) who participated in a 4-wave longitudinal study, spaced 12 months apart. The results of cross-lagged panel modeling (i.e. CLPM) found the significant bidirectional relations between parental harsh punishment and psychoticism at the between-family level. However, the within-person level analysis of random intercept cross-lagged panel modeling (i.e. RI-CLPM) only revealed parental harsh punishment significantly predicted youth psychoticism, but not vice versa. Moreover, no sex differences were observed in the bidirectional relations between parental harsh punishment and psychoticism at the between- or within-family level. These results suggest parental harsh parenting could exacerbate the psychoticism trait at both the between- and within-family level, whereas the influence of young people's psychoticism on harsh parenting response from parents occurs only at the between-family level. The findings help to understand the nature of the dynamic process of change between psychoticism and harsh parenting among Chinese adolescents.

Social Anxiety and Peer Victimization and Aggression: Examining Reciprocal Trait-State Effects among Early Adolescents.

As peer relationships become paramount during early adolescence, there's a normative rise in social anxiety, coinciding with a peak in peer victimization and aggression. Although previous studies have suggested reciprocal associations between changes in social anxiety and adolescent peer victimization and aggression, the mechanics of these associations at the personal trait and time-varying state levels remains unclear. This study examined the longitudinal relations between social anxiety and adolescent peer victimization and aggression by disentangling between-person trait differences from within-person state processes. A total of 4731 Chinese early adolescents (44.9% girls; M age = 10.91 years, SD = 0.72) participated in a four-wave longitudinal study with 6-month intervals. Random-intercept cross-lagged panel model (RI-CLPM) was applied. The results revealed higher levels of social anxiety are associated with more peer victimization and aggression at the between-person trait level. At the within-person state level, adolescent social anxiety, and adolescent physical victimization and physical aggression, reciprocally predicted each other. Relational victimization significantly predicted an increase of social anxiety, but not vice versa. Social anxiety positively predicted relational aggression over time, whereas the effect of relational aggression on social anxiety was only observed at the initial stage of early adolescence. These findings highlight that various types of victimization and aggression might exhibit unique reciprocal associations with social anxiety. Distinguishing between the within-person state and between-person trait effects is crucial in research that informs the co-development of adolescent peer victimization, aggression, and social anxiety.

The vicious cycle of family dysfunction and problematic gaming and the mediating role of self-concept clarity among early adolescents: A within-person analysis using random intercept cross-lagged panel modeling.

Backgrounds and aims: Family dysfunction is a significant risk factor for adolescent problematic gaming, yet few studies have investigated the bidirectional relations between changes in family dysfunction and adolescent problematic gaming and potential mediating mechanisms. This study thus examined the bidirectional relations between family dysfunction and adolescent problematic gaming and the mediating role of self-concept clarity within this relation. Methods: Participants included 4,731 Chinese early adolescents (44.9% girls; M age = 10.91 years, SD = 0.72) who were surveyed at four time points 6 months apart. Results: Random intercept cross-lagged panel modeling found (a) family dysfunction directly predicts increased problematic gaming, (b) adolescent problematic gaming directly predicts increased experience of family dysfunction, (c) family dysfunction indirectly predicts problematic gaming via self-concept clarity, and (d) adolescent problematic gaming indirectly predicts family dysfunction via self-concept clarity. Discussion and conclusions: The present study suggests that adolescents may be trapped in a vicious cycle between family dysfunction and problematic gaming either directly or indirectly through impairing their self-concept clarity. Findings indicate fostering youth self-concept clarity is essential to break the vicious circle between dysfunctional experiences in the family and problematic gaming among adolescents.

Brown Slime Cap Mushroom (Chroogomphus rutilus, Agaricomycetes) Polysaccharide Resists Motion Sickness by Inhibiting the Activity of the Serotonin System in Mice.

Motion sickness (MS) is a disorder of the autonomic nervous system caused by abnormal exercise with symptoms such as nausea, vomiting and drowsiness. More than 90% of the human population has experienced different degrees of MS. At present, anticholinergics, antihistamines, and sympathomimetic drugs are used for treating MS, but these drugs generally have some adverse reactions and are not suitable for all people. Therefore, it is necessary to develop anti-MS drugs that have high efficiency and no adverse effects. Previous studies have found that Chroogomphus rutilus polysaccharide (CRP) is effective at preventing and treating MS in rats and mice. However, its mechanism of action is not clear. To clarify whether the CRP has anti-MS effects in mice, and to clarify its mechanism, we performed behavioral, biochemical, and morphological tests in a Kunming mouse model. Our results indicate that CRPs can significantly relieve the symptoms of MS, and their effect is equivalent to that of scopolamine, a commonly used anti-MS medicine. Our results indicate that CRPs may directly act on the gastrointestinal chromaffin cells to inhibit the synthesis and release of serotonin (5-hydroxytryptamine, or 5-HT) and thus reduce the signal from the gastrointestinal tract.

"Etiology of trichiasis/distichiasis and its management with CO2 laser ablation".

BACKGROUND: Many techniques have been used to treat trichiasis/distichiasis, but none of them are consistently successful, without complications, or effective in different severities. Additionally, etiologic factors and their relationship with the severity or prognosis has not been identified in non-trachoma-endemic area. METHODS: In this retrospective consecutive study, we enrolled patients with trichiasis or distichiasis who had undergone CO2 laser ablation in our tertiary medical center between November 2013 and May 2022. Surgical success was defined as no regrowth of misdirected eyelashes for at least 3 months postoperatively. We recorded the success rate within three months and one year after one treatment session, and within three treatment sessions. We also investigated the relationship between etiologic factors, severity, and the success rate. RESULTS: We enrolled 216 eyelids of 137 patients (average age: 69.4 years, mean follow-up durations: 22.9 months). The major underlying causes of trichiasis/distichiasis were idiopathic (64.4%) and prior eyelid surgery (20.8%). More major trichiasis/distichiasis was observed among patients aged <60 years than that in patients aged ≥60 years (43% vs. 21%, p<0.01), and among patients with an underlying cause of prior eyelid surgery compared to patients with idiopathic etiology (42.2% vs. 23.0%, p<0.01). The success rates within three months and within one year after one treatment session, and within three treatment sessions were 87.5%, 76.2%, and 94.4%. CONCLUSIONS: Our study demonstrated idiopathic etiology and prior eyelid surgery are common causes of trichiasis/distichiasis. CO2 laser ablation is a safe, effective, and efficient treatment modality.

Talaromyces amestolkiae Infection in an AIDS Patient with Cryptococcal Meningitis.

Concurrent infections caused by multiple fungal pathogens in immunocompromised patients can pose diagnostic and treatment challenges. Here, we presented the first reported case in Taiwan of an AIDS patient who had concurrent infection with Cryptococcus neoformans meningitis and Talaromyces amestolkiae lymphadenopathy. The patient presented with an enlarged inguinal lymph node and was diagnosed with T. amestolkiae lymphadenitis. The species T. amestolkiae was identified using DNA sequencing, which had the capability of differentiating it from other Talaromyces species. The patient was discharged from the hospital following treatment with amphotericin B and subsequent administration of voriconazole. This case highlights the importance of maintaining a suspicion of co-infections and utilizing appropriate diagnostic tools, such as DNA sequencing, to identify possible pathogens. Further studies are needed to determine the optimal treatment for T. amestolkiae and other co-infecting fungal pathogens.

Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant. OBJECTIVE: To evaluate acute kidney injury risk associated with intravitreal anti-VEGF drugs in patients with retinal diseases. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials on 12 July, 2023, and included randomized controlled trials reporting acute kidney injury between anti-VEGF drugs (e.g., aflibercept, bevacizumab, brolucizumab, and ranibizumab) and controls for retinal diseases (e.g., age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy/diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization). Data were synthesized by a fixed-effects model for pooling odds ratios (ORs) using the Peto method. RESULTS: We included 13 randomized controlled trials (four and nine trials for aflibercept and ranibizumab, respectively) with a total of 4282 participants. The meta-analysis indicated intravitreal anti-VEGF drugs did not increase the acute kidney injury risk, compared with controls (odds ratio [OR]: 1.00, 95% confidence interval [CI] 0.49-2.04, I2: 0%), and no differences in the acute kidney injury risk were observed between different anti-VEGF drugs (OR: 1.10, 95% CI 0.27-4.43, I2: 0% for aflibercept; OR: 0.97, 95% CI 0.42-2.22, I2: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07-284.13, I2: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42-1.93, I2: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16-15.88, I2: 0% for retinal vein occlusion). CONCLUSIONS: Intravitreal anti-VEGF drugs were not associated with an acute kidney injury risk, regardless of which anti-VEGF drugs (aflibercept or ranibizumab) or retinal diseases (age-related macular degeneration, diabetic retinopathy/diabetic macular edema, or retinal vein occlusion) were involved. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42021267854.

Clinical metagenomics-assisted diagnosis of relapsed HIV-associated cryptococcal meningitis.

To date, the identification of crypotococcal relapse remains clinically challenging as it often has similar manifestation with paradoxical immune reconstitution inflammatory syndrome. This study reports on the use of metagenomics assisted next generation sequencing to aid in diagnosing recurrent cryptococcal meningitis in an person living with HIV experiencing recurring symptoms, despite negative culture results for Cryptococcus neoformans in the cerebrospinal fluid. Although fungal culture was negative, when reads from metagenomic and metatranscriptomic sequencing performed on the Day 308 cerebrospinal fluid sample were mapped onto the genome from the Day 4 isolate, 589 specific reads were identified. NCBI BLAST search also revealed Cryptococcus-specific 18S/25S/28S ribosomal RNA, indicating a relapse of the disease.

Violent Video Game Exposure and Cyberbullying in Early Adolescents: A Latent Moderated Mediation Model.

Violent video game exposure (VVGE) is a significant predictor of adolescent cyberbullying perpetration. However, little is known about the mediating and moderated mechanisms between them. This study examined the mediating role of moral disengagement between VVGE and cyberbullying perpetration as well as the moderating role of callous-unemotional (CU) traits on those associations. A total of 2,523 Chinese adolescents (Mage = 13.22, SD = 1.60, 48.4 percent girls) participated this study. Structural equation modeling showed that VVGE was significantly related to cyberbullying perpetration and moral disengagement play a mediating role between them. Latent moderated structural equation modeling showed that CU traits strengthened the effect of VVGE on moral disengagement and of VVGE on cyberbullying perpetration. Results further showed that the mediating effect of moral disengagement was more prominent for youths who have higher levels of CU traits. Interventions to reduce moral disengagement and CU traits among adolescents may interrupt the effect of VVGE to cyberbullying perpetration.

The Impact of the COVID-19 Pandemic on Respiratory Syncytial Virus Infection: A Narrative Review.

Respiratory syncytial virus (RSV) is one of the most common respiratory viruses. It not only affects young children but also the elderly and immunocompromised patients. After the emergence of SARS-CoV-2 and the corona virus disease 2019 (COVID-19) era, a dramatic reduction in RSV activity was found, which coincided with the implementation of public health and social measures (PHSMs). However, the correlation is more complicated than we initially thought. After PHSMs were gradually lifted, a seasonality shift and a delayed RSV outbreak with greater number of infected patients were found in numerous countries, such as Israel, Australia, South Africa, New Zealand, France, United States, and Japan. Several hypotheses and possible reasons explaining the interaction between SARS-CoV-2 and RSV were mentioned. Since RSV vaccinations are still under investigation, administration of palivizumab should be considered in high-risk patients. In the post-COVID-19 era, greater attention should be paid to a further resurgence of RSV. In this narrative review, we conducted a thorough review of the current knowledge on the epidemiology of RSV during the COVID-19 era, the out-of-season outbreak of RSV, and the data on co-infection with RSV and SARS-CoV-2.

Extraction Optimization and Antioxidant Activities of Ethanol Extract of the Brown Roll-Rim Mushroom Paxillus involutus (Agaricomycetes).

Box Behnken design (BBD) was used to optimize the extraction of Paxillus involutus (EPI) in ethanol. The optimum extraction conditions were as follows: temperature 45°C; solid:liquid ratio 1:35; time 5 h. Under these conditions, the yield of EPI was 13.57%. The antioxidant activity of EPI was evaluated in vitro, and DPPH free radical scavenging, ABTS free radical scavenging, and hydroxyl free radical scavenging effects were found to be equal to or close to that of the positive control vitamin C (VC). The antioxidant activity of EPI was next evaluated in vivo using aging mice; it was found to have appreciable effect on scavenging malonic dialdehyde (MDA) and could increase the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and total superoxide dismutase (T-SOD) in mice. Overall, EPI showed antioxidant effects in aging mice, thereby delaying aging, and has potential for application as a natural antioxidant and in medical applications.

Blood Culture Negative Endocarditis: A Review of Laboratory Diagnostic Approaches.

Infective endocarditis is a potentially fatal condition, and identifying the pathogen is crucial to optimizing antibiotic treatment. While a blood culture takes time and may yield negative results, it remains the gold standard for diagnosis, blood culture-negative endocarditis, which accounts for up to 20% of infective endocarditis cases, poses a clinical challenge with increasing mortality. To better understand the etiology of blood culture-negative infective endocarditis, we reviewed non-culture-based strategies and compared the results. Serology tests work best in limited pathogens, such as Coxiella burnetii and Bartonella infections. Most of the pathogens identified by broad-range PCR tests are Streptococcus spp, Staphylococcus spp and Propionibacterium spp. adding specific real-time PCR assays to the systematic PCR testing of patients with blood culture-negative endocarditis will increase the efficiency of diagnosis. Recently, metagenomic next-generation sequencing has also shown promising results.

Double-Needle Haptic Repositioning: A Troubleshooting Technique for Flanged Intraocular Lens Fixation.

PURPOSE: Haptic repositioning during flanged intraocular lens (IOL) fixation can be difficult, and the haptic requiring repositioning may be at increased risk of excessive bending or breakage. This study aimed to report double-needle haptic repositioning technique outcomes for the aforementioned difficulty during flanged IOL fixation. METHODS: This retrospective case series included seven eyes requiring haptic repositioning during flanged IOL fixation. The method features reinsertion of an already externalized haptic into the needle lumen followed by a needle-haptic complex internalized through the original tract into the eyeball. Thus, an adequate configuration for contralateral haptic can be achieved for insertion into the needle lumen to create a double-needle condition before both haptics are successfully externalized. RESULTS: The median follow-up duration was 24 months (range, 4-24 months). Postoperatively, the IOL was well-centered, and corrected distance visual acuity improved from 20/320 (20/4,000-20/70) to 20/50 (20/250-20/20). No intraoperative or postoperative complications were noted. CONCLUSION: The technique produced encouraging results in patients undergoing haptic repositioning during flanged IOL fixation. This technique could potentially reduce haptic overbending risk and facilitate haptic adjustment. Further studies are needed to confirm the feasibility of the technique.

A systematic approach to reduce intraocular pressure for the treatment of glaucoma.

Glaucoma is the leading cause of irreversible blindness due to increased intraocular pressure (IOP) in the eye. We have developed a novel treatment option for glaucoma based on a real-time IOP-dependent nitric oxide synthase (NOS) and packed in a therapeutic contact lens to reduce the IOP. First, 1.6 nmole nitric oxide was produced from the genetic chassis, which was optimized for isopropyl ß-d-1-thiogalactopyranoside (IPTG) induction in a T7 expression system. For biosafety concerns to human being, the csgAD genes responsible for curli biofilm formation in Escherichia coli were co-expressed with NOS in the designated NOSAD strain to strengthen the adherence of cells to the contact lens, thereby preventing the contamination into the eyes. Moreover, NOSAD is a diaminopimelic acid (DAP) auxotrophic strain, which cannot survive without supplementation of DAP and reached the critical consideration of biosafety to the environment. We also demonstrated that the nitric oxide diffusion was 3.6-times enhanced from penetration into the aqueous humor of porcine eyes. The deformation ratio of the contact lens was correlated to the change of IOP by using a digital image correlation (DIC) system in a porcine eye model. The novel systematic approach provides an alternative treatment for glaucoma patients in the future.

Hypoglycemic Activity of Total Flavonoids from Slippery Jack Mushroom, Suillus luteus (Agaricomycetes), In Vitro and In Vivo.

The hypoglycemic effects of total flavonoids from Suillus luteus (SLFLA) were investigated in vitro and in vivo. The glucose consumption experiment in HepG2 cells showed that SLFLA had hypoglycemic activity in vitro. Moreover, SLFLA could improve insulin resistance and exhibited good hypoglycemic activity in the insulin resistance model. In streptozotocin-induced diabetic mice, SLFLA could effectively reduce blood sugar, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase levels. Damage to the liver, kidney, and pancreas in diabetic mice was mitigated after intragastric administration of SLFLA. These results suggested that SLFLA might be a promising functional food or medicine for T2DM treatment.

Iso-suillin-induced DNA damage leading to cell cycle arrest and apoptosis arised from p53 phosphorylation in A549 cells.

Extensive investigations have revealed that iso-suillin, a secondary metabolite isolated from Suillus flavus, could induce cell cycle arrest and apoptosis in human chronic myeloid leukemia K562 cells, human hepatocellular carcinoma SMMC-7721 cell line, and human small cell lung cancer H446 cell line in vitro. In the present study, human lung cancer A549 cells were used to reveal the mechanism of iso-suillin's effects on lung adenocarcinoma, which were detected both in vitro and in vivo. Results showed that iso-suillin potently inhibited A549 cell proliferation through an early G1 arrest. Iso-suillin also induced A549 cell apoptosis in vitro. Phosphorylation of p53 at serines 15 and 20 may be one of the pivotal factors for cell cycle arrest and apoptosis after treatment of iso-suillin in A549 cells. Moreover, in an A549 xenograft model, tumor growth and progression could be inhibited by iso-suillin. Body weight change and some vital organs toxicity was also roughly examined, no significant toxic effects of iso-suillin were shown (at a dose of 5 mg/kg for each administration). The in vitro and in vivo anti-tumor effects implied that iso-suillin may act as a tumor growth inhibitor, and its induction of p53 phosphorylation is pivotal for cell cycle arrest and apoptosis in A549 cells.

Novel hypoglycemic compounds from wild mushroom Paxillus involutus.

Wild mushrooms are an important source of secondary metabolites possessing a broad range of biological activities. In this study, eight new compounds, named furanopaxin A-F (1-6), deoxybisinvolutone (7), and coumarinvol (8) along with two known compounds were isolated from fruiting bodies of the wild mushroom Paxillus involutus (Batsch) Fr. Their structures were established based on HR-ESI-MS and 1D and 2D NMR spectroscopic data. The results of hypoglycemic assays indicated that compounds 5-8 possessed significant α-glucosidase inhibitory activities, with IC50 values ranging from 14.65 ± 1.68 to 47.55 ± 1.47 µM, and each compound could enhance glucose consumption in insulin-resistance HepG2 cells. Further analysis by molecular docking implied that compounds 5-8 could interact with the amino acid residues of α-glucosidase, supporting the hypoglycemic activity of the compounds.

Novel 2,5-Diarylcyclopentenone Derivatives from the Wild Edible Mushroom Paxillus involutus and Their Antioxidant Activities.

Wild edible mushrooms are important as a source of nutraceuticals and for the discovery of bioactive metabolites as pharmaceuticals. In this work, 10 rare 2,5-diarylcyclopentenone derivatives were isolated from the wild edible mushroom Paxillus involutus (Batsch) Fr., including eight novel compounds termed involutenone A-H (1-8) and two previously identified compounds (9-10). Their structures were established using high-resolution electrospray ionization mass spectroscopy and 1D and 2D nuclear magnetic resonance data. The absolute configurations of compounds 1-3 and 6-8 were assigned based on the comparison of the experimental and calculated electronic circular dichroism data. The antioxidant activities of 1-8 were tested through DPPH free radical scavenging, hydroxyl radical scavenging, and superoxide anion radical scavenging assays. Compounds 3, 5, 6, and 7 demonstrated significant antioxidant activity compared to the positive control (tert-butylhydroquinone). These compounds could be effective natural antioxidants with considerable pharmaceutical value.