Alkaline shock protein 23 (Asp23)-controlled cell wall imbalance promotes membrane vesicle biogenesis in Staphylococcus aureus.

Membrane vesicles (MVs) are produced by species across all domains of life and have diverse physiological functions as well as promising applications. While the mechanisms for vesiculation in Gram-negative bacteria are well-established, the genetic determinants and regulatory factors responsible for MV biogenesis in Gram-positive bacteria remain largely unknown. Here, we demonstrate that a Q225P substitution in the alternative sigma factor B (SigB) triggers MV production in Staphylococcus aureus strain Newman by hindering the specific binding of SigB to the asp23 promoter, thereby repressing expression of alkaline shock protein 23 (Asp23). Isogenic deletion of asp23 also promotes MV formation in Newman, confirming the critical roles played by sigB and asp23 in modulating S. aureus vesiculation. While bacterial growth and cytoplasmic membrane fluidity are not impaired, mutation of asp23 weakens the cell wall and enhances autolysis, consistent with decreased expression of alpha-type psm and lrgAB that modulate murein hydrolase activity. TEM and proteomic analysis show that Newman and asp23 deletion mutant generate MVs with nearly identical morphology and composition, but virulence-associated factors are significantly enriched in MVs from the asp23 mutant. Overall, this study reveals novel genetic determinants underlying S. aureus vesiculation and advances the understanding of the physiology of MV biogenesis in S. aureus.

Multiparametric simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) incorporating intratumoral and peritumoral regions for grading of glioma.

Background: Preoperative grading gliomas is essential for therapeutic clinical decision-making. Current non-invasive imaging modality for glioma grading were primarily focused on magnetic resonance imaging (MRI) or positron emission tomography (PET) of the tumor region. However, these methods overlook the peritumoral region (PTR) of tumor and cannot take full advantage of the biological information derived from hybrid-imaging. Therefore, we aimed to combine multiparameter from hybrid 18F-fluorodeoxyglucose (18F-FDG) PET/MRI of the solid component and PTR were combined for differentiating high-grade glioma (HGG) from low-grade glioma (LGG). Methods: A total of 76 patients with pathologically confirmed glioma (41 HGG and 35 LGG) who underwent simultaneous 18F-FDG PET, arterial spin labelling (ASL), and diffusion-weighted imaging (DWI) with hybrid PET/MRI were retrospectively enrolled. The relative maximum standardized uptake value (rSUVmax), relative cerebral blood flow (rCBF), and relative minimum apparent diffusion coefficient (rADCmin) for the solid component and PTR at different distances outside tumoral border were compared. Receiver operating characteristic (ROC) curves were applied to assess the grading performance. A nomogram for HGG prediction was constructed. Results: HGGs displayed higher rSUVmax and rCBF but lower rADCmin in the solid component and 5 mm-adjacent PTR, lower rADCmin in 10 mm-adjacent PTR, and higher rCBF in 15- and 20-mm-adjacent PTR. rSUVmax in solid component performed best [area under the curve (AUC) =0.865] as a single parameter for grading. Combination of rSUVmax in the solid component and adjacent 20 mm performed better (AUC =0.881). Integration of all 3 indicators in the solid component and adjacent 20 mm performed the best (AUC =0.928). The nomogram including rSUVmax, rCBF, and rADCmin in the solid component and 5-mm-adjacent PTR predicted HGG with a concordance index (C-index) of 0.906. Conclusions: Multiparametric 18F-FDG PET/MRI from the solid component and PTR performed excellently in differentiating HGGs from LGGs. It can be used as a non-invasive and effective tool for preoperative grade stratification of patients with glioma, and can be considered in clinical practice.

Exact dispersion relation of the quantum Langmuir wave.

The normal modes, i.e., the eigensolutions to the dispersion relation equation, are the most fundamental properties of a plasma. The real part indicates the intrinsic oscillation frequency while the imaginary part the Landau damping rate. In most of the literature, the normal modes of quantum plasmas are obtained by means of small damping approximation, which is invalid for high-k modes. In this paper, we solve the exact dispersion relations via the analytical continuation scheme, and, due to the multi-value nature of the Fermi-Dirac distribution, reformation of the complex Riemann surface is required. It is found that the topological shape of the root locus in quantum plasmas is quite different from classical ones, in which both real and imaginary frequencies of high-k modes increase with k steeper than the typical linear behavior in classical plasmas. As a result, the time-evolving behavior of a high-k initial perturbation becomes ballistic-like in quantum plasmas.

Analysis of blasting vibration duration considering frequency and energy and its application.

Blasting vibration's effect on ground vibration is essentially an energy transfer and transformation process (Hongtao et al., 2010) [1]. In engineering, the blasting vibration duration is often used as an objective index to evaluate the blasting vibration hazard. Thus, this study on the factors influencing blasting vibration duration is essential. In this study, the blasting vibration duration prediction formula uses frequency and energy as independent parameters, which are analysed using a statistical t probability distribution. With the blasting vibration duration prediction formula, the delay time taken for the structure to reach the resonance frequency is obtained by calculating the dominant frequency of the structure. The results indicate that the frequency and energy of the blasting vibration signal are highly correlated with the duration of blasting vibration, and their introduction as independent parameters in the prediction formula can better improve the prediction accuracy. The dominant frequency should not be neglected in blasting vibration safety evaluations, and the use of blasting vibration duration prediction to calculate the dominant frequency can better avoid the resonance phenomenon in the structure.

Flavonoidal alkaloids: Emerging targets for drug discovery from Nature's bounty.

This paper explores the potential of flavonoid alkaloids, a unique class of compounds that contain both flavonoid and alkaloid structures, as emerging targets for drug discovery. These compounds exhibit diverse biological activities, such as anti-inflammatory, anti-cancer, and anti-diabetic effects, which are attributed to the combination of different flavonoid scaffolds and alkaloid groups. Flavonoid alkaloids have attracted researchers' attention due to their diverse structures and important bio-activities. Therefore, this review summarizes recent advances in the extraction, purification, structural characterization, synthesis pathways and biological activities of flavonoid alkaloids from natural sources. Finally, the potential prospects and challenges associated with this class of compounds in pharmacological research are discussed along with details of a mechanistic investigation and future clinical applications in this research field.

Effects of Different Cultivation Modes on Morphological Traits and Correlations between Traits and Body Mass of Crayfish (Procambarus clarkii).

In this study, juvenile crayfish hatched from the same population were cultured in different growing environments: pond (D1), paddy field (D2), and aquaculture barrel (D3), and fed for 60 days. Crayfishes were selected randomly, females and males, 50 tails each from six groups (D1-♀, D1-♂, D2-♀, D2-♂, D3-♀, D3-♂) to measure the following morphological traits: full length (X1), body length (X2), chelicerae length (X3), chelicerae weight (X4), cephalothorax length (X5), cephalothorax width (X6), cephalothorax height (X7), eye spacing (X8), caudal peduncle length (X9), and caudal peduncle weight (X10). We found that the coefficient of variation (CV) of X4 was the largest in each culture mode, and males (28.58%~38.67%) were larger than females (37.76%~66.74%). The CV of X4 of crayfish cultured in D1 and D2 was larger than that of D3. All traits except X8 were positively correlated with body weight (p < 0.05). After pathway analysis, we found that X4, X5, X7, and X10 were significantly correlated with the body weight of D1-♀; the equation was YD1-♀ = -29.803 + 1.249X4 + 0.505X5 + 0.701X7 + 1.483X10 (R2 = 0.947). However, X2, X4, and X6 were significantly correlated with the body weight of D1-♂; the equation was YD1-♂ = -40.881 + 0.39X2 + 0.845X4 + 1.142X6 (R2 = 0.927). In D2-♀, X1, X4, X5, and X10 were significantly correlated with body weight; the equation was YD2-♀ = -12.248 + 0.088X1 + 1.098X4 + 0.275X5 + 0.904X10 (R2 = 0.977). X4 and X5 played a major role in the body weight of D2-♂ with the equation: YD2-♂ = -24.871 + 1.177X4 + 0.902X5 (R2 = 0.973). X3 and X10 mainly contributed to the body weight of D3-♀ with the equation: YD3-♀ = -22.476 + 0.432X3 + 3.153X10 (R2 = 0.976). X1 and X4 mainly contributed to the body weight of D3-♂ with the equation: YD3-♂ = -34.434 + 0.363X1 + 0.669X4 (R2 = 0.918). Comparing the pathway analysis with the gray relation analysis, we could conclude that the traits most correlated with body weight in D1-♀ were X10 and X7; in D1-♂, X6; in D2-♀, X10, X1, and X5; in D2-♂, X5; in D3-♀, X10; and in D3-♂, X4 and X1.

Pulmonary tumor thrombotic microangiopathy: Two case reports and literature review.

RATIONALE: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy. PATIENT CONCERNS: Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension. DIAGNOSES: One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy. INTERVENTIONS: The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause. OUTCOMES: Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm. LESSONS: PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis.

Nanomedicines targeting activated immune cells and effector cells for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and inflammatory cellular infiltration. Functional cells in the RA microenvironment (RAM) are composed of activated immune cells and effector cells. Activated immune cells, including macrophages, neutrophils, and T cells, can induce RA. Effector cells, including synoviocytes, osteoclasts, and chondrocytes, receiving inflammatory stimuli, exacerbate RA. These functional cells, often associated with the upregulation of surface-specific receptor proteins and significant homing effects, can secrete pro-inflammatory factors and interfere with each other, thereby jointly promoting the progression of RA. Recently, some nanomedicines have alleviated RA by targeting and modulating functional cells with ligand modifications, while other nanoparticles whose surfaces are camouflaged by membranes or extracellular vesicles (EVs) of these functional cells target and attack the lesion site for RA treatment. When ligand-modified nanomaterials target specific functional cells to treat RA, the functional cells are subjected to attack, much like the intended targets. When functional cell membranes or EVs are modified onto nanomaterials to deliver drugs for RA treatment, functional cells become the attackers, similar to arrows. This study summarized how diversified functional cells serve as targets or arrows by engineered nanoparticles to treat RA. Moreover, the key challenges in preparing nanomaterials and their stability, long-term efficacy, safety, and future clinical patient compliance have been discussed here.

Candidatus Liberibacter asiaticus influences the emergence of the Asian citrus psyllid Diaphorina citri by regulating key cuticular proteins.

The Asian citrus psyllid, Diaphorina citri, is the primary vector of the HLB pathogen, Candidatus Liberibacter asiaticus (CLas). The acquisition of CLas shortens the developmental period of nymphs, accelerating the emergence into adulthood and thereby facilitating the spread of CLas. Cuticular proteins (CPs) are involved in insect emergence. In this study, we investigated the molecular mechanisms underlying CLas-promoted emergence in D. citri via CP mediation. Here, a total of 159 CP genes were first identified in the D. citri genome. Chromosomal location analysis revealed an uneven distribution of these CP genes across the 13 D. citri chromosomes. Proteomic analysis identified 54 differentially expressed CPs during D. citri emergence, with 14 CPs exhibiting significant differential expression after CLas acquisition. Five key genes, Dc18aa-1, Dc18aa-2, DcCPR-24, DcCPR-38 and DcCPR-58, were screened from the proteome and CLas acquisition. The silencing of these 5 genes through a modified feeding method significantly reduced the emergence rate and caused various abnormal phenotypes, indicating the crucial role that these genes play in D. citri emergence. This study provides a comprehensive overview of the role of CPs in D. citri and reveals that CLas can influence the emergence process of D. citri by regulating the expression of CPs. These key CPs may serve as potential targets for future research on controlling huanglongbing (HLB) transmission.

Unraveling the mechanism of thermotolerance by Set302 in Cryptococcus neoformans.

The underlying mechanism of thermotolerance, which is a key virulence factor essential for pathogenic fungi such as Cryptococcus neoformans, is largely unexplored. In this study, our findings suggest that Set302, a homolog of Set3 and a subunit of histone deacetylase complex Set3C, contributes to thermotolerance in C. neoformans. Specifically, the deletion of the predicted Set3C core subunit, Set302, resulted in further reduction in the growth of C. neoformans at 39°C, and survival of transient incubation at 50°C. Transcriptomics analysis revealed that the expression levels of numerous heat stress-responsive genes altered at both 30°C and 39°C due to the lack of Set302. Notably, at 39°C, the absence of Set302 led to the downregulation of gene expression related to the ubiquitin-proteasome system (UPS). Based on the GFP-α-synuclein overexpression model to characterize misfolded proteins, we observed a pronounced accumulation of misfolded GFP-α-synuclein at 39°C, consequently inhibiting C. neoformans thermotolerance. Furthermore, the loss of Set302 exacerbated the accumulation of misfolded GFP-α-synuclein during heat stress. Interestingly, the set302∆ strain exhibited a similar phenotype under proteasome stress as it did at 39°C. Moreover, the absence of Set302 led to reduced production of capsule and melanin. set302∆ strain also displayed significantly reduced pathogenicity and colonization ability compared to the wild-type strain in the murine infection model. Collectively, our findings suggest that Set302 modulates thermotolerance by affecting the degradation of misfolded proteins and multiple virulence factors to mediate the pathogenicity of C. neoformans.IMPORTANCECryptococcus neoformans is a pathogenic fungus that poses a potential and significant threat to public health. Thermotolerance plays a crucial role in the wide distribution in natural environments and host colonization of this fungus. Herein, Set302, a critical core subunit for the integrity of histone deacetylase complex Set3C and widely distributed in various fungi and mammals, governs thermotolerance and affects survival at extreme temperatures as well as the formation of capsule and melanin in C. neoformans. Additionally, Set302 participates in regulating the expression of multiple genes associated with the ubiquitin-proteasome system (UPS). By eliminating misfolded proteins under heat stress, Set302 significantly contributes to the thermotolerance of C. neoformans. Moreover, Set302 regulates the pathogenicity and colonization ability of C. neoformans in a murine model. Overall, this study provides new insight into the mechanism of thermotolerance in C. neoformans.

[Exploration of mechanism of total triterpenoids from fruits of Chaenomeles speciosa against senescent GES-1 cells induced by D-galactose based on Gln/GLS1/α-KG metabolic axis and mitochondrial apoptosis signaling pathway].

Total triterpenoids from the fruits of Chaenomeles speciosa(TCS) are active components in the prevention and treatment of gastric mucosal damage, which have potential anti-aging effects. However, it is still unclear whether TCS can improve gastric aging, especially its molecular mechanism against gastric aging. On this basis, this study explored the effect and mechanism of TCS on senescent GES-1 cells induced by D-galactose(D-gal) to provide scientific data for the clinical use of TCS to prevent gastric aging. GES-1 cells cultured in vitro and those transfected with overexpression GLS1(GLS1-OE) plasmid of glutaminase 1(GLS1) were induced to aging by D-gal, and then TCS and or GLS1 inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide(BPTES) were given. Cell survival rate, positive rate of ß-galactosidase(SA-ß-gal) staining, mitochondrial membrane potential(MMP), and apoptosis were investigated. GLS1 activity, levels of glutamine(Gln), glutamate(Glu), α-ketoglutarate(α-KG), urea, and ammonia in supernatant and cells were detected by enzyme-linked immunosorbent assay(ELISA) and colorimetric methods. The mRNA and protein expressions of GLS1 and the related genes of the mitochondrial apoptosis signaling pathway were measured by real-time fluorescence quantitative PCR and Western blot. The results manifested that compared with the D-gal model group and GLS1-OE D-gal model group, TCS significantly decreased the SA-ß-gal staining positive cell rate and MMP of D-gal-induced senescent GES-1 cells and GLS1-OE senescent GES-1 cells, inhibited the survival of senescent cells, and promoted their apoptosis(P<0.01). It decreased the activity of GLS1 and the content of Gln, Glu, α-KG, urea, and ammonia in supernatant and cell(P<0.01), reduced the concentration of cytochrome C(Cyto C) in mitochondria and the mRNA and protein expressions of GLS1 and proliferating nuclear antigen in cells(P<0.01). The mRNA expression of Bcl-2 and Bcl-xl, the protein expression of pro-caspase-9 and pro-caspase-3, and the ratio of Bcl-2/Bax and Bcl-xl/Bad in cells were decreased(P<0.01). Cyto C concentration in the cytoplasm, the mRNA expressions of Bax, Bad, apoptosis protease activating factor 1(Apaf-1), and protein expressions of cleaved-caspase-9, cleaved-caspase-3, cleaved-PARP-1 were increased(P<0.01). The aforementioned results indicate that TCS can counteract the senescent GES-1 cells induced by D-gal, and its mechanism may be closely related to suppressing the Gln/GLS1/α-KG metabolic axis, activating the mitochondrial apoptosis pathway, and thereby accelerating the apoptosis of the senescent cells and eliminating senescent cells.

PCSK9 aggravated carotid artery stenosis in ApoE-/- mice by promoting the expression of tissue factors in endothelial cells via the TLR4/NF-κB pathway.

Atherosclerosis, a chronic inflammatory disease, is the most relevant cause of carotid artery stenosis. Vascular endothelial cells (ECs) play a significant role in the development of atherosclerosis. In this chronic inflammatory environment, we aimed to investigate whether PCSK9 could mitigate atherosclerosis progression by reducing tissue factor expression in ECs via in vivo and in vitro assays. In vivo, we investigated the effect of PCSK9 inhibition on preventing atherosclerotic lesion formation in ApoE-/- mice fed a western diet. The results showed that inhibiting PCSK9 could significantly downregulate the protein expression of tissue factor (TF) in ECs to reduce the area of atherosclerotic plaques. In vitro, we incubated human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS). We found that LPS-induced TF elevation was suppressed by a PCSK9 inhibitor at both the mRNA and protein levels and that the TLR4/NF-κB pathway was also suppressed by a PCSK9 inhibitor. With respect to plasma samples from patients with carotid artery stenosis, we also demonstrated that the expression of TF was positively correlated with that of PCSK9. Thus, in addition to regulating lipid metabolism, the regulation of endothelial cell TF expression through the TLR4/NF-κB pathway may be a potential mechanism of PCSK9 in promoting atherosclerotic carotid stenosis.

Overexpression of an Integument Esterase Gene LbEST-inte4 Infers the Malathion Detoxification in Liposcelis bostrychophila (Psocoptera: Liposcelididae).

Liposcelis bostrychophila, commonly known as booklouse, is an important stored-product pest worldwide. Studies have demonstrated that booklices have developed resistance to several insecticides. In this study, an integument esterase gene, LbEST-inte4, with upregulated expression, was characterized in L. bostrychophila. Knockdown of LbEST-inte4 resulted in a substantial increase in the booklice susceptibility to malathion. Overexpression of LbEST-inte4 in Drosophila melanogaster significantly enhanced its malathion tolerance. Molecular modeling and docking analysis suggested potential interactions between LbEST-inte4 and malathion. When overexpressed LbEST-inte4 in Sf9 cells, a notable elevation in esterase activity and malathion tolerance was observed. HPLC analysis indicated that the LbEST-inte4 enzyme could effectively degrade malathion. Taken together, the upregulated LbEST-inte4 appears to contribute to malathion tolerance in L. bostrychophila by facilitating the depletion of malathion. This study elucidates the molecular mechanism underlying malathion detoxification and provides the foundations for the development of effective prevention and control measures against psocids.

Polydopamine-modified black phosphorus nanosheet drug delivery system for the treatment of ischemic stroke.

Black phosphorus (BP), as a representative metal-free semiconductor, has been extensively explored. It has a higher drug loading capacity in comparison to conventional materials and also possesses excellent biocompatibility and biodegradability. Furthermore, BP nanosheets can enhance the permeability of the blood-brain barrier (BBB) upon near-infrared (NIR) irradiation, owing to their photothermal effect. However, the inherent instability of BP poses a significant limitation, highlighting the importance of surface modification to enhance its stability. Ischemic stroke (IS) is caused by the occlusion of blood vessels, and its treatment is challenging due to the hindrance caused by the BBB. Therefore, there is an urgent need to identify improved methods for bypassing the BBB for more efficient IS treatment. This research devised a novel drug delivery approach based on pterostilbene (Pte) supported by BP nanosheets, modified with polydopamine (PDA) to form BP-Pte@PDA. This system shows robust stability and traverses the BBB using effective photothermal mechanisms. This enables the release of Pte upon pH and NIR stimuli, offering potential therapeutic advantages for treating IS. In a middle cerebral artery occlusion mouse model, the BP-Pte@PDA delivery system significantly reduced infarct size, and brain water content, improved neurological deficits, reduced the TLR4 inflammatory factor expression, and inhibited cell apoptosis. In summary, the drug delivery system fabricated in this study thus demonstrated good stability, therapeutic efficacy, and biocompatibility, rendering it suitable for clinical application.

Investigating Immunotoxicity in Black Carp (Mylopharyngodon piceus) Fingerlings Exposed to Niclosamide.

Niclosamide (NIC) is a potent salicylanilide molluscicide/helminthicide commonly utilized for parasite and mollusc control in aquatic environments. Due to its persistent presence in water bodies, there is growing concern regarding its impact on aquatic organisms, yet this remains inadequately elucidated. Consequently, this study aims to assess the hepatotoxic effects and detoxification capacity of black carp (Mylopharyngodon piceus) in a semi-static system, employing various parameters for analysis. NIC was applied to juvenile black carp at three different concentrations (0, 10 and 50 µg/L) for 28 days in an environmentally realistic manner. Exposure to 50 µg/L NIC resulted in an increase in hepatic lysozyme (LYZ), alkaline phosphatase (ALP), and complement 4 (C4) levels while simultaneously causing a decrease in peroxidase (POD) activity. Additionally, NIC exposure exhibited a dose-dependent effect on elevating serum levels of LYZ, ALP, complement 3 (C3), C4, and immunoglobulin T (IgT). Notably, the mRNA levels of immune-related genes tnfα, il8, and il6, as well as nramp and leap2, were upregulated in fish exposed to NIC. RNA-Seq analysis identified 219 differentially expressed genes (DEGs) in M. piceus after NIC exposure, with 94 upregulated and 125 downregulated genes. KEGG and GO analyses showed enrichment in drug metabolism pathways and activities related to oxidoreductase, lip oprotein particles, and cholesterol transport at 50 µg/L NIC. Additionally, numerous genes associated with lipid metabolism, oxidative stress, and innate immunity were upregulated in NIC-exposed M. piceus. Taken together, these findings indicate that NIC has the potential to cause hepatotoxicity and immunotoxicity in M. piceus. This research offers important insights for further understanding the impact of molluscicide/helminthicide aquatic toxicity in ecosystems.

Distinct Changes in Metabolic Profile and Sensory Quality with Different Varieties of Chrysanthemum (Juhua) Tea Measured by LC-MS-Based Untargeted Metabolomics and Electronic Tongue.

Chrysanthemum tea, a typical health tea with the same origin as medicine and food, is famous for its unique health benefits and flavor. The taste and sensory quality of chrysanthemum (Juhua) tea are mainly determined by secondary metabolites. Therefore, the present research adopted untargeted metabolomics combined with an electronic tongue system to analyze the correlation between the metabolite profiles and taste characteristics of different varieties of chrysanthemum tea. The results of sensory evaluation showed that there were significant differences in the sensory qualities of five different varieties of chrysanthemum tea, especially bitterness and astringency. The results of principal component analysis (PCA) indicated that there were significant metabolic differences among the five chrysanthemum teas. A total of 1775 metabolites were identified by using untargeted metabolomics based on UPLC-Q-TOF/MS analysis. According to the variable importance in projection (VIP) values of the orthogonal projections to latent structures discriminant analysis (OPLS-DA), 143 VIP metabolites were found to be responsible for metabolic changes between Huangju and Jinsi Huangju tea; among them, 13 metabolites were identified as the key metabolites of the differences in sensory quality between them. Kaempferol, luteolin, genistein, and some quinic acid derivatives were correlated with the "astringency" attributes. In contrast, l-(-)-3 phenyllactic acid and L-malic acid were found to be responsible for the "bitterness" and "umami" attributes in chrysanthemum tea. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the flavonoid and flavonol biosynthesis pathways had important effects on the sensory quality of chrysanthemum tea. These findings provide the theoretical basis for understanding the characteristic metabolites that contribute to the distinctive sensory qualities of chrysanthemum tea.

A young woman with Mycobacterium chelonae complex infection caused by facial stem cell injection.

In outpatient settings, Mycobacterium chelonae complex infection brought on by cosmetic injections are rather uncommon. We came across a case of infection brought on by a commercial stem cell injection.

A Flavonoid Glycoside Compound from Siraitia grosvenorii with Anti-Inflammatory and Hepatoprotective Effects In Vitro.

Inflammation is a pivotal factor in the development and advancement of conditions like NAFLD and asthma. Diet can affect several phases of inflammation and significantly influence multiple inflammatory disorders. Siraitia grosvenorii, a traditional Chinese edible and medicinal plant, is considered beneficial to health. Flavonoids can suppress inflammatory cytokines, which play a crucial role in regulating inflammation. In the present experiments, kaempferol 3-O-α-L-rhamnoside-7-O-ß-D-xylosyl(1→2)-O-α-L-rhamnoside (SGPF) is a flavonoid glycoside that was first isolated from S. grosvenorii. A series of experimental investigations were carried out to investigate whether the flavonoid component has anti-inflammatory and hepatoprotective effects in this plant. The researchers showed that SGPF has a stronger modulation of protein expression in LPS-induced macrophages (MH-S) and OA-induced HepG2 cells. The drug was dose-dependent on cells, and in the TLR4/NF-κB/MyD88 pathway and Nrf2/HO-1 pathway, SGPF regulated all protein expression. SGPF has a clear anti-inflammatory and hepatoprotective function in inflammatory conditions.

Preparation of nano-silver containing black phosphorus based on quaternized chitosan hydrogel and evaluating its effect on skin wound healing.

Hydrogels with favorable biocompatibility and antibacterial properties are essential in postoperative wound hemorrhage care, facilitating rapid wound healing. The present investigation employed electrostatic adsorption of black phosphorus nanosheets (BPNPs) and nano­silver (AgNPs) to cross-link the protonated amino group NH3+ of quaternized chitosan (QCS) with the hydroxyl group of hyaluronic acid (HA). The electrostatic interaction between the two groups resulted in the formation of a three-dimensional gel network structure. Additionally, the hydrogel containing AgNPs deposited onto BPNPs was assessed for its antibacterial properties and effects on wound healing. Hydrogel demonstrated an outstanding drug-loading capacity and could be employed for wound closure. AgNPs loaded on the BPNPs released silver ions and exhibited potent antibacterial properties when exposed to 808 nm near-infrared (NIR) radiation. The ability of the hydrogel to promote wound healing in an acute wound model was further evaluated. The BPNPs were combined with HA and QCS in the aforementioned hydrogel system to improve adhesion, combine the photothermal and antibacterial properties of the BPNPs, and promote wound healing. Therefore, the reported hydrogels displayed excellent biocompatibility and hold significant potential for application in the field of tissue engineering for skin wound treatment.

TGF-ß1-triggered BMI1 and SMAD2 cooperatively regulate miR-191 to modulate bone formation.

Transforming growth factor ß 1 (TGF-ß1), as the most abundant signaling molecule in bone matrix, is essential for bone homeostasis. However, the signaling transduction of TGF-ß1 in the bone-forming microenvironment remains unknown. Here, we showed that microRNA-191 (miR-191) was downregulated during osteogenesis and further decreased by osteo-favoring TGF-ß1 in bone marrow mesenchymal stem cells (BMSCs). MiR-191 was lower in bone tissues from children than in those from middle-aged individuals and it was negatively correlated with collagen type I alpha 1 chain (COL1A1). MiR-191 depletion significantly increased osteogenesis and bone formation in vivo. Hydrogels embedded with miR-191-low BMSCs displayed a powerful bone repair effect. Mechanistically, transcription factors BMI1 and SMAD2 coordinately controlled miR-191 level. In detail, BMI1 and pSMAD2 were both upregulated by TGF-ß1 under osteogenic condition. SMAD2 activated miR-191 transcription, while BMI1 competed with SMAD2 for binding to miR-191 promoter region, thus disturbing the activation of SMAD2 on miR-191 and reducing miR-191 level. Altogether, our findings reveal that miR-191 regulated by TGF-ß1-induced BMI1 and SMAD2 negatively modulated bone formation and regeneration, and inhibition of miR-191 might be therapeutically useful to enhance bone repair in clinic.