Association between social media use and depressive symptoms in middle-aged and older Chinese adults.

The burden of depressive symptoms among middle-aged and older Chinese during the COVID-19 pandemic is unclear, and the contribution of social media use to depressive symptoms in this population has not been studied. To address the gaps, we analyzed data from the China Health and Retirement Longitudinal Study, nationally representative biannual surveys among adults aged ≥45 years. Social media use and depressive symptoms were measured in the 2018 and 2020 surveys. We tested longitudinal associations between baseline (2018) social media activities and risk of depressive symptoms in two years among 9121 participants without depressive symptoms. We also evaluated whether social media activity could reduce depressive symptoms during this period among 5302 individuals with depressive symptoms at baseline. Depressive symptoms affected 36·0% of this population in 2020. Women, individuals living in rural areas, and residents of western China provinces were particularly affected. Among participants without depressive symptoms, engaging in social media activities at baseline was associated with a 24.0% (95% confidence interval [CI]: 10-36%) lower likelihood of developing depressive symptoms over the next two years. Among depressed participants, compared to individuals not using social media, those initiating three or more social media activities during this period had 1.24 (95% CI: 1.05-1.46) times higher chance of becoming non-depressed, and those using social media all the time were 1·36 (95% CI: 1·09-1·72) times more likely to become non-depressed. In conclusion, middle-aged and older Chinese adults have a substantial burden of depressive symptoms, and social media activities may help to prevent and reduce the symptoms.

Sedimentary provenance supports a mid-paleozoic tectonic connection between the Junggar and Altai terranes in central Asia.

The provenance of Precambrian detritus in the Junggar and Altai terranes provides crucial constraints on the peri-Siberian accretionary tectonic evolution in the middle Paleozoic. The Precambrian detrital zircons have no coeval magmatic equivalents in the Junggar terrane but show U-Pb age spectra and εHf(t) values comparable to those in the Altai terrane. The correlations suggest that the old detrital materials in the Junggar and Altai terranes were most likely derived from the Siberia craton and adjacent Tuva-Mongolian microcontinent. Paleozoic zircons in the Junggar terrane display a εHf(t) pattern from large spread to dominantly positive values at ca. 420-410 Ma. Such an abrupt change points to an accretionary tectonic transition from an advancing to retreating mode during mid-Paleozoic time, synchronous with similar tectonic switch occurring in the Altai terrane. Taking into account the temporal and spatial relations in sedimentation, tectonism and arc magmatism, we propose that the Junggar terrane had once collided onto the peri-Siberian Altai terrane to receive abundant old detritus from the Siberian continent in the Silurian-early Devonian. They were subsequently separated at ca. 420-410 Ma, possibly due to the slab rollback of the subducting Paleo-Asian Ocean (PAO) plate. These results constrain an Early Paleozoic tectono-paleogeographic boundary of the CAOB along the North Tianshan-Solonker suture zone, and also imply a long-lived PAO subduction was responsible for the Neoproterozoic to Paleozoic accretionary orogenesis at the margins of southern Siberia, eastern Kazakhstan, and northern Gondwana.

Noise Exposure Promotes Alzheimer's Disease-Like Lesions and DNA Damage.

OBJECTIVE: This study aimed to explore the mechanism by which noise contributes to the development of Alzheimer's disease (AD)-like lesions. METHOD: Male Wistar rats (24 months) were allocated into two groups (n = 6 per groups): a noise group exposed to 98 dB sound pressure-level white noise for 4 hours daily from 8:00 to 12:00 for 30 days, and a control group without noise exposure. The cognitive functions of the rats were assessed using new-object recognition and Morris water maze tests. Then, hippocampal tissues were collected, and the levels of amyloid ß 1-42 (Aß1-42), Aß1-40, brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) were measured using enzyme-linked immunosorbent assay (ELISA). Protein expression was evaluated through Western blot. RESULTS: Noise exposure significantly impaired cognitive and recognition abilities, increased the escape latency, and decreased the number of crossings through the platform quadrant intersection and the time spent in the target quadrant (P < 0.01). The new-object exploration and recognition index of the rats in the noise group markedly decreased (P < 0.01). ELISA results indicated increases in Aß1-40 and Aß1-42 levels and decreases in BDNF and TrkB levels in the rat hippocampus in the noise group (P < 0.01). Western blot analyses revealed that beta-site amyloid precursor protein (APP) cleaving enzyme 1, phosphorylated tau protein, gamma-H2A histone family, member X, checkpoint kinase 2, p53, and p21 were remarkably elevated in the noise group (P < 0.01). CONCLUSION: Chronic noise exposure can cause hippocampal genetic damage in aged rats, leading to cognitive disorders and the development of lesions similar to those observed in AD. Thus, noise is a potential risk factor for neurodegenerative disorders.

Discovery, development and optimisation of a novel frog antimicrobial peptide with combined mode of action against drug-resistant bacteria.

Antimicrobial peptides (AMP) have emerged as promising candidates for addressing the clinical challenges posed by the rapid evolution of antibiotic-resistant microorganisms. Brevinins, a representative frog-derived AMP family, exhibited broad-spectrum antimicrobial activities, attacking great attentions in previous studies. However, their strong haemolytic activity and cytotoxicity, greatly limit their further development. In this work, we identified and characterised a novel brevinin-1 peptide, brevinin-1pl, from the skin secretions of the northern leopard frog, Rana pipiens. Like many brevinins, brevinin-1pl also displayed strong haemolytic activity, resulting in a lower therapeutic index. We employed several bioinformatics tools to analyse the structure and potential membrane interactions of brevinin-1pl, leading to a series of modifications. Among these analogues, des-Ala16-[Lys4]brevinin-1pl exhibited great enhanced therapeutic efficacy in both in vitro and in vivo tests, particularly against some antibiotics-resistant Escherichia coli strains. Mechanistic studies suggest that des-Ala16-[Lys4]brevinin-1pl may exert bactericidal effects through multiple mechanisms, including membrane disruption and DNA binding. Consequently, des-Ala16-[Lys4]brevinin-1pl holds promise as a candidate for the treatment of drug-resistant Escherichia coli infections.

Effectiveness of a home-based, post-discharge early intervention program for very preterm infants in reducing parental stress: a randomized controlled trial.

BACKGROUND: This study aims to evaluate the impact of a home-based, post-discharge early intervention (EI) program on reducing parental stress levels in families with preterm infants born between 28+ 0 and 31+ 6 weeks gestational age. METHODS: A randomized controlled trial was conducted, with families randomly allocated to either the EI or standard care (SC) group. A term reference group was also recruited for comparison. The Parental Stress Index-Short Form was used to assess parental stress levels, yielding a total stress score and three subdomain scores. Assessment was performed at baseline, at the 60-day mark of the study, and when the infants reached six corrected months of age. Parents in the reference group were assessed only at six months of corrected age for infants. The intervention comprised three sections: intellectual, physical, and social training, which was administered to the infants in the EI group immediately after discharge and to those in the SC group after 60 days of enrollment. RESULTS: Seventy-three families were enrolled in this study, with 37 allocated to the EI group, and 36 to the SC group. Prior to intervention, higher stress levels were reported by mothers in both groups than fathers, with no difference observed between the EI and SC groups. Re-assessment performed at 60 days of the study showed that mothers and fathers in the EI group had significantly lower total stress score than those in the SC group (82.00 ± 5.64 vs. 94.26 ± 7.99, p < 0.001; 80.74 ± 7.14 vs. 89.94 ± 9.17, p < 0.001, respectively), which was predominantly due to the lower scores in parental distress and parental-child dysfunction interaction subdomains in the EI group (both had p < 0.001). Mothers in the EI group exhibited a more pronounced reduction in total stress score after intervention when compared to fathers (13.15 ± 4.68 vs. 8.26 ± 4.03, p < 0.001). At six months of infant age, the total stress score and subdomain scores of parents in the EI and SC groups were similar, but significantly higher than those of the reference group. CONCLUSION: The home-based, post-discharge EI program demonstrated significant effectiveness in reducing parental stress levels among the parents of very preterm infants. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (registration number: CTR1900028330). Registration date: December 19, 2019.

[Tempo-spatial Variations in Nitrogen and Phosphorus Loads in Jianli-Hankou Reach of the Middle Yangtze River During the Past 20 Years].

Ammonia nitrogen （NH4+-N） and total phosphorus （TP） were the major control pollutants in the Yangtze River Basin. Based on measured data from 2003 to 2020, the temporal and spatial variations in concentrations and fluxes of NH4+-N and TP in the Jianli to Hankou （JL-HK） reach of the Middle Yangtze River were studied, and the impacts of flow-sediment factors, tributary inflows, and others on variations in NH4+-N and TP fluxes were discussed. The results showed that： ① In recent years, NH4+-N and TP concentrations in the mainstream have declined significantly, with annual NH4+-N and TP concentrations at each monitoring station in 2020 averagely decreasing by 41% and 34% compared to those in 2003, respectively. Spatially, NH4+-N and TP concentrations decreased and then increased along the mainstream. NH4+-N and TP concentrations of tributary inflows, which include the Dongting Lake and Han River, were generally lower than that of the mainstream. The multi-year average values of NH4+-N and TP concentrations were both averaged at 0.12 mg·L-1 in the mainstream and were averaged at 0.11 mg·L-1 and 0.09 mg·L-1 in the tributary inflows. ② The flux differences between the upper and lower sections net of tributary confluences showed that NH4+-N and TP fluxes were lost in the Jianli to Luoshan （JL-LS） sub-reach and increased in the Luoshan to Hankou （LS-HK） sub-reach in most years. NH4+-N and TP fluxes decreased in the JL-LS sub-reach, which was related to the lower NH4+-N and TP concentrations in lateral inflows, such as Dongting Lake, and thus lowered the NH4+-N and TP concentrations in the mainstream. The LS-HK sub-reach showed the opposite trends, and the water and sediment loads increased in this sub-reach. Across the whole JL-HK reach, TP flux as well as water and sediment loads were recharged along the reach, whereas NH4+-N flux was reduced greatly, which could be attributed to the pollution abatement conducted in the Yangtze River Basin, which mainly focused on NH4+-N. ③ The correlation analysis results showed that NH4+-N fluxes had the strongest correlation with NH4+-N concentrations but not significantly correlated with discharges and sediment transport rates, indicating that NH4+-N was mainly controlled by point source pollution in the study reach. TP fluxes had higher correlations with discharges and sediment transport rates in high flow level periods, and the correlations between TP fluxes and TP concentrations were better in low flow level periods, reflecting that point source pollution contributed more to TP in dry seasons compared to flood seasons.

Apolipoprotein E deficiency exacerbates blood-brain barrier disruption and hyperglycemia-associated hemorrhagic transformation after ischemic stroke.

BACKGROUND: The polymorphism of the apolipoprotein E (ApoE) gene has been implicated in both the susceptibility to neurodegenerative disease and the prognosis of traumatic brain injury (TBI). However, the influence of ApoE on the risk of hemorrhagic transformation (HT) after acute ischemic stroke remains inconclusive. The present study aimed to investigate the potential impact of ApoE deficiency on the risk of hyperglycemia-associated HT and to elucidate the underlying mechanisms. METHODS: Wild-type (WT) and ApoE knockout (ApoE-/-) mice were injected with 50 % glucose to induce hyperglycemia and subsequently subjected to 90 min of intraluminal middle cerebral artery occlusion (MCAO). The mortality, neurological function, HT incidence and HT grading-score were evaluated at 24 hours after reperfusion. To evaluate the integrity of blood-brain barrier (BBB), the immunoglobulin G (IgG) leakage and the protein expressions of tight junctions (TJs) were detected using immunofluorescent staining and western blotting. Finally, the levels of matrix metalloproteinases (MMP)-2/9, microglial activation and proinflammatory mediators were investigated using immunofluorescent staining and western blotting. RESULTS: ApoE-/- mice exhibited increased mortality and exacerbated neurological impairment, concomitant with more severe hyperglycemia-associated HT 24 hours post-reperfusion. Meanwhile, ApoE deficiency exacerbated the disruption of BBB, characterized by increased leakage of IgG, aggravated degradation of TJs and microvascular basement membranes. Furthermore, ApoE deficiency further aggravated the upregulation of MMP-2/9 and microglia-triggered neuroinflammation. CONCLUSIONS: Our findings demonstrate that the absence of ApoE exacerbates neurological impairment and hyperglycemia-associated HT in ischemic stroke mice, which is closely associated with MMP-2/9 signaling and neuroinflammation-mediated disruption of BBB.

Effect of blockage of Trem1 on the M1 polarization of macrophages in the regulation dental pulp inflammation.

Dental pulp inflammation is a common and significant factor related to poor dental prognosis. Current treatment strategies primarily concentrate on managing the inflammatory response, with specific targets for intervention still under investigation. Triggering receptors expressed on myeloid cells (TREMs) are a group of receptor molecules extensively present on myeloid cell surfaces, crucial in the regulation of inflammatory process. Our analysis of transcriptomic sequencing data from clinical pulp samples of dataset GSE77459 and animal models revealed up-regulation of Trem1 during pulpitis. Administration of the Trem1-blocking peptide LP17 led to lower (more than 1-fold) levels of several pro-inflammatory factors and inhibition of M1 macrophage polarization both in vivo and in vitro. This study of the expression patterns and functions of Trem1 in the development of dental pulp inflammation provides novel insights into the therapeutic strategies for clinical pulpitis.

Exosome-transmitted circ_0004664 suppresses the migration and invasion of cadmium-transformed human bronchial epithelial cells by regulating PTEN expression via miR-942-5p.

Exosomes play a crucial role in regulating extracellular communication between normal and cancer cells within the tumor microenvironment, thereby affecting tumor progression through their cargo molecules. However, the specific impact of exosomal circular RNAs (circRNAs) on the development of cadmium-induced carcinogenesis remains unclear. To address this, we investigated whether exosomes derived from normal human bronchial epithelial BEAS-2B (N-B2B) cells could transmit circRNA to cadmium-transformed BEAS-2B (Cd-B2B) cells and the potential effects on Cd-B2B cells. Our findings demonstrated a significant downregulation of circ_0004664 in Cd-B2B cells compared to N-B2B cells (P < 0.01). Overexpression of circ_0004664 in Cd-B2B cells led to a significant inhibition of cell migration and invasion (P < 0.01 or P < 0.05). Furthermore, N-B2B cells could transfer circ_0004664 into recipient Cd-B2B cells via exosomes, subsequently inhibiting cell migration and invasion (P < 0.05 or P < 0.01). Mechanistic investigations revealed that exosomal circ_0004664 functioned as a competitive endogenous RNA for miR-942-5p, resulting in an upregulation of PTEN (P < 0.05). Our study highlights the involvement of exosomal circ_0004664 in cell-cell communication during cadmium carcinogenesis, providing a novel insight into the role of exosomal circRNA in this process.

Enhancement of Antimicrobial Function by L/D-Lysine Substitution on a Novel Broad-Spectrum Antimicrobial Peptide, Phylloseptin-TO2: A Structure-Related Activity Research Study.

Antibiotic resistance poses a serious threat to public health globally, reducing the effectiveness of conventional antibiotics in treating bacterial infections. ESKAPE pathogens are a group of highly transmissible bacteria that mainly contribute to the spread of antibiotic resistance and cause significant morbidity and mortality in humans. Phylloseptins, a class of antimicrobial peptides (AMPs) derived from Phyllomedusidae frogs, have been proven to have antimicrobial activity via membrane interaction. However, their relatively high cytotoxicity and low stability limit the clinical development of these AMPs. This project aims to study the antimicrobial activity and mechanisms of a phylloseptin-like peptide, phylloseptin-TO2 (PSTO2), following rational amino acid modification. Here, PSTO2 (FLSLIPHAISAVSALAKHL-NH2), identified from the skin secretion of Phyllomedusa tomopterna, was used as the template for modification to enhance antimicrobial activity. Adding positive charges to PSTO2 through substitution with L-lysines enhanced the interaction of the peptides with cell membranes and improved their antimicrobial efficacy. The analogues SRD7 and SR2D10, which incorporated D-lysines, demonstrated significant antimicrobial effects against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) while also showing reduced haemolytic activity and cytotoxicity, resulting in a higher therapeutic index. Additionally, SRD7, modified with D-lysines, exhibited notable anti-proliferative properties against human lung cancer cell lines, including H838 and H460. This study thus provides a potential development model for new antibacterial and anti-cancer drugs combating antibiotic resistance.

Discovery and engineering of a novel peptide, Temporin-WY2, with enhanced in vitro and in vivo efficacy against multi-drug resistant bacteria.

Infections by drug-resistant microorganisms are a threat to global health and antimicrobial peptides are considered to be a new hope for their treatment. Temporin-WY2 was identified from the cutaneous secretion of the Ranidae frog, Amolops wuyiensis. It presented with a potent anti-Gram-positive bacterial efficacy, but its activity against Gram-negative bacteria and cancer cell lines was unremarkable. Also, it produced a relatively high lytic effect on horse erythrocytes. For further improvement of its functions, a perfect amphipathic analogue, QUB-1426, and two lysine-clustered analogues, 6K-WY2 and 6K-1426, were synthesised and investigated. The modified peptides were found to be between 8- and 64-fold more potent against Gram-negative bacteria than the original peptide. Additionally, the 6K analogues showed a rapid killing rate. Also, their antiproliferation activities were more than 100-fold more potent than the parent peptide. All of the peptides that were examined demonstrated considerable biofilm inhibition activity. Moreover, QUB-1426, 6K-WY2 and 6K-1426, demonstrated in vivo antimicrobial activity against MRSA and E. coli in an insect larvae model. Despite observing a slight increase in the hemolytic activity and cytotoxicity of the modified peptides, they still demonstrated a improved therapeutic index. Overall, QUB-1426, 6K-WY2 and 6K-1426, with dual antimicrobial and anticancer functions, are proposed as putative drug candidates for the future.

Functional characterisation and modification of a novel Kunitzin peptide for use as an anti-trypsin antimicrobial peptide against drug-resistant Escherichia coli.

In recent decades, antimicrobial peptides (AMPs) have emerged as highly promising candidates for the next generation of antibiotic agents, garnering significant attention. Although their potent antimicrobial activities and ability to combat drug resistance make them stand out among alternative agents, their poor stability has presented a great challenge for further development. In this work, we report a novel Kunitzin AMP, Kunitzin-OL, from the frog Odorrana lividia, exhibiting dual antimicrobial and anti-trypsin activities. Through functional screening and comparison with previously reported Kunitzin peptides, we serendipitously discovered a unique motif (-KVKF-) and unveiled its crucial role in the antibacterial functions of Kunitzin-OL by modifying it through motif removal and duplication. Among the designed derivatives, peptides 4 and 8 demonstrated remarkable antimicrobial activities and low cytotoxicity, with high therapeutic index (TI) values (TI4 = 20.8, TI8 = 20.8). Furthermore, they showed potent antibacterial efficacy against drug-resistant Escherichia coli strains and exhibited lipopolysaccharide (LPS)-neutralising activity, effectively alleviating LPS-induced inflammatory responses. Overall, our findings provide a new short motif for designing effective AMP drugs and highlight the potential of the Kunitztin trypsin inhibitory loop as a valuable motif for the design of AMPs with enhancing proteolytic stability.

Macrogenomic and Metabolomic Analyses Reveal Mechanisms of Gut Microbiota and Microbial Metabolites in Diarrhea of Weaned Piglets.

Recent studies have shown a correlation between piglet diarrhea and the gut microbiota. However, the precise mechanism by which intestinal microorganisms and their metabolites influence diarrhea in weaned piglets remains unclear. This study explored differences in the gut microbiota and associated metabolites between healthy and diarrheic-weaned piglets using macrogenomic and metabolomic analyses. The histomorphological results showed that diarrheic piglets had shorter jejunal and ileal villi, some of which were shed, compared to healthy piglets. Substantial differences in gut microbial diversity and metabolites were also observed, with Bacteroidaceae bacterium and Caudoviricetes being the main differential organisms that were strongly correlated with host status. Microbial functions, mainly the metabolism of carbohydrates, glycans, lipids, and amino acids, as well as related enzyme activities, were substantially different. The major differential metabolites were carnosine, pantothenic acid (vitamin B5), pyridoxal, methylimidazoleacetic acid, indole-3-acetaldehyde, and 5-hydroxyindoleacetic acid. These metabolites were enriched in beta-alanine, histidine, tryptophan, and vitamin B6 metabolism, and in the pantothenate and CoA biosynthesis pathways. Combined macrogenomic and metabolomic analyses revealed that carnosine, vitamin B5, and pyridoxal were negatively correlated with Caudoviricetes; methylimidazoleacetic acid, indole-3-acetaldehyde, and 5-hydroxyindoleacetic acid were positively correlated with Caudoviricetes. Whereas carnosine and vitamin B5 were positively correlated with Bacteroidaceae bacterium, 5-hydroxyindoleacetic acid was negatively correlated. The decreased abundance of Bacteroidaceae bacterium and the increased abundance of Caudoviricetes and related metabolites likely contribute to post-weaning diarrhea in piglets. Therefore, the abundance of Bacteroidaceae bacterium and Caudoviricetes can likely serve as potential markers for identifying and preventing diarrhea in post-weaning piglets.

Complement C3a/C3aR inhibition alleviates the formation of aortic aneurysm in Marfan syndrome mice.

Mutations in fibrillin 1 (FBN1) is the main cause of Marfan syndrome (MFS) with thoracic aortic aneurysm (TAA) as the main complication. Activation of the complement system plays a key role in the formation of thoracic and abdominal aortic aneurysms. However, the role of the complement system in MFS-associated aortic aneurysms remains unclear. In this study, we observed increased levels of complement C3a and C5a in the plasma of MFS patients and mouse, and the increased deposition of the activated complement system product C3b/iC3b was also observed in the elastic fiber rupture zone of 3-month-old MFS mice. The expression of C3a receptor (C3aR) was increased in MFS aortas, and recombinant C3a promoted the expression of cytokines in macrophages. The administration of a C3aR antagonist (C3aRA) attenuated the development of thoracic aortic aneurysms in MFS mice. The increased inflammation response and matrix metalloproteinases activities were also attenuated by C3aRA treatment in MFS mice. Therefore, these findings indicate that the complement C3a/C3aR inhibition alleviates the formation of aortic aneurysm in Marfan syndrome mice.

N6-methyladenosine facilitates arsenic-induced neoplastic phenotypes of human bronchial epithelial cells by promoting miR-106b-5p maturation.

Arsenic is a widespread carcinogen and an important etiological factor for lung cancer. Dysregulated miRNAs have been implicated in arsenic carcinogenesis and the mechanisms of arsenic-induced dysregulated miRNAs have not been fully elucidated. N6-methyladenosine (m6A) modification is known to modulate pri-miRNA processing. However, whether m6A-mediated pri-miRNA processing is involved in arsenic carcinogenesis is poorly understood. Here, we found that m6A modification was significantly increased in arsenite-transformed human bronchial epithelial BEAS-2B cells (0.5 µM arsenite, 16 weeks). Meanwhile, METTL3 was significantly upregulated at week 12 and 16 during cell transformation. The proliferation, migration, invasion, and anchorage-independent growth of arsenite-transformed cells were inhibited by the reduction of m6A levels through METTL3 knockdown. Further experiments suggest that the oncogene miR-106b-5p is a potentially essential m6A target mediating arsenic-induced lung cancer. miR-106b-5p was observed to be upregulated after exposure to arsenite for 12 and 16 weeks, and the reduction of m6A levels caused by METTL3 knockdown inhibited miR-106b-5p maturation in arsenite-transformed cells. What's more, miR-106b-5p overexpression successfully rescued METTL3 knockdown-induced inhibition of the neoplastic phenotypes of transformed cells. Additionally, Basonuclin 2 (BNC2) was uncovered as a potential target of miR-106b-5p and downregulated by METTL3 via enhancing miR-106b-5p maturation. Additionally, the METTL3 inhibitor STM2457 suppressed neoplastic phenotypes of arsenite-transformed BEAS-2B cells by blocking pri-miR-106b methylation. These results demonstrate that m6A modification promotes the neoplastic phenotypes of arsenite-transformed BEAS-2B cells through METTL3/miR-106b-5p/BNC2 pathway, providing a new prospective for understanding arsenic carcinogenesis.

Medicaid Coverage in Early Childhood for Children With Sickle Cell Disease.

This cohort study examines patterns of Medicaid coverage in the first 3 years of life among children with sickle cell disease across 5 states.

Analysis of the role of dihydromyricetin derived from vine tea (Ampelopsis grossedentata) on multiple myeloma by activating STAT1/RIG-I axis.

Multiple myeloma (MM) is a plasma cell malignancy and remains incurable as it lacks effective curative approaches; thus, novel therapeutic strategies are desperately needed. The study aimed to explore the therapeutic role of dihydromyricetin (DHM) in MM and explore its mechanisms. Human MM and normal plasma samples, human MM cell lines, and normal plasma cells were used for in vitro experiments. Cell counting kit-8 (CCK-8), flow cytometry, and trans-well assays were performed for the assessment of cell viability, apoptosis, migration, and invasion, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the mRNA expression of signal transducer and activator of transcription 1 (STAT1) and retinoic acid-inducible gene I (RIG-I). Western blotting was employed to assess E-cadherin, N-cadherin, signal transducer, STAT1, p-STAT1, and RIG-I protein expression. A tumor xenograft model was used for in vivo experiments. Here, dihydromyricetin (DHM) dose-dependently restrained viability, apoptosis, migration, and invasion, and facilitated apoptosis of U266 cells. After DHM treatment, the E-cadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells, suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition (EMT) in MM. Besides, the levels of p-STAT1/STAT1 and RIG-I were down-regulated in MM. However, the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 cells. Also, DHM inhibited MM tumor growth and EMT, and activated STAT1/RIG-I pathway in vivo. Collectively, this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling, which provides a novel drug for the treatment of MM.

Modification and Synergistic Studies of a Novel Frog Antimicrobial Peptide against Pseudomonas aeruginosa Biofilms.

The overuse of traditional antibiotics has resulted in bacterial resistance and seriously compromised the therapeutic efficacy of traditional antibiotics, making the exploration of new antimicrobials particularly important. Several studies have shown that bioactive peptides have become an important source of new antimicrobial drugs due to their broad-spectrum antibacterial action and lack of susceptibility to resistance. In this study, a novel bioactive peptide Nigrosin-6VL was characterised from the skin secretion of the golden cross band frog, Odorrana andersonii, by using the 'shotgun' cloning strategy. Modifications on the Rana Box of Nigrosin-6VL revealed its critical role in antimicrobial functions. The peptide analogue, 2170-2R, designed to preserve the Rana Box structure while enhancing cationicity, exhibited improved therapeutic efficacy, particularly against Gram-negative bacteria, with a therapeutic value of 45.27. Synergistic studies demonstrated that 2170-2R inherits the synergistic antimicrobial activities of the parent peptides and effectively enhances the antimicrobial capacity of cefepime and gentamicin against both planktonic cells and biofilms. Specifically, 2170-2R can synergise effectively with cefepime and gentamicin against different strains of P. aeruginosa biofilms. Consequently, 2170-2R holds promise as a potent antimicrobial agent developed to combat infections induced by Pseudomonas aeruginosa.

Network Medicine: A Potential Approach for Virtual Drug Screening.

Traditional drug screening methods typically focus on a single protein target and exhibit limited efficiency due to the multifactorial nature of most diseases, which result from disturbances within complex networks of protein-protein interactions rather than single gene abnormalities. Addressing this limitation requires a comprehensive drug screening strategy. Network medicine is rooted in systems biology and provides a comprehensive framework for understanding disease mechanisms, prevention, and therapeutic innovations. This approach not only explores the associations between various diseases but also quantifies the relationships between disease genes and drug targets within interactome networks, thus facilitating the prediction of drug-disease relationships and enabling the screening of therapeutic drugs for specific complex diseases. An increasing body of research supports the efficiency and utility of network-based strategies in drug screening. This review highlights the transformative potential of network medicine in virtual therapeutic screening for complex diseases, offering novel insights and a robust foundation for future drug discovery endeavors.

Emergency department 30-Day emergency department revisits among people with sickle cell disease: Variations in characteristics.

People with sickle cell disease (SCD) often have emergency department (ED) revisits. The characteristics of people with SCD with ED revisits were assessed in this study using Medicaid administrative claims data from California and Georgia, representing 2794 and 3641 individuals with SCD, respectively. In both states, those with 6+ primary care provider (PCP) encounters had the highest percentage of ED revisits. In California, those with 6+ hematology encounters had the lowest percentage of individuals with an ED revisit; in Georgia, those with 1-2 hematology encounters. Increasing access to hematologic care may reduce ED revisits among people with SCD.