Experimental study on H2O2 activation of HSC-T6 and hepatic fibrosis in cholestatic mice by "Yajieshaba".

ETHNOPHARMACOLOGICAL RELEVANCE: Yajieshaba (YJSB), approved by the Yunnan Provincial Food and Drug Administration in 2008, are known for their anti-inflammatory, antiviral, and pro-apoptotic properties, effectively treating Hepatic fibrosis (HF). However, its mechanism of action remains unclear. AIM OF THE STUDY: The objective of this investigation is to explore how YJSB influences the TGF-ß1/Smad signaling pathway as a strategy for reducing HF. METHODS: The establishment of a HF model in mice involved ligation of the common bile duct, followed by administration of YJSB. Body and liver weights were measured, and the liver index calculated. Serum levels of ALT, AST, ALP, TBA, and TBIL were assessed using colorimetric methods. Additionally, liver homogenates were analyzed for PIIINP, Col-IV, LN, HA, and Hyp, as well as TGF-ß1 activity, using ELISA. Histological analyses of liver sections, stained with H&E, Ag, and Masson's trichrome, were performed to examine inflammation and the accumulation of collagen and reticular fibers. These studies aimed to elucidate the pharmacodynamic effects of YJSB on HF in mice with bile duct obstruction. The target pathways of YJSB were preliminarily identified through immunofluorescence detection of TGF-ß1, P-Smad2L, P-Smad2C, P-Smad3L, P-Smad3C, and Smad4 proteins. In vitro experiments included the induction of hepatic stellate cell (HSC-T6) activation by H2O2. A cell injury model was established for HSC-T6, and the CCK-8 assay was used to determine the optimal YJSB concentration and treatment duration. After pirfenidone (PFD) administration, which inhibits the TGF-ß1/Smad pathway, the effects of YJSB on HSC-T6 cell proliferation were observed. ELISA assays quantified Col-III, α-SMA, and Col-I in cell lysates to assess YJSB's impact on collagen synthesis in HSC-T6 cells. Western blot analysis was performed to assess the protein levels within the TGF-ß1/Smad signaling cascade. RESULTS: In the HF mouse model, administration of YJSB notably augmented the body weight and reduced the liver index. Concurrently, there was an elevation in serum concentrations of ALP, AST, ALT, TBA, and TBIL. Similarly, in the liver homogenates of HF mice, increases were observed in the levels of HA, PIIINP, Col-IV, LN, Hyp, and TGF-ß1. Histological assessments using H&E, Ag, and Masson stains indicated a substantial diminution in liver tissue damage. Through immunofluorescence analysis, it was discerned that YJSB modulated the expression of TGF-ß1, P-Smad2L, P-Smad2C, and P-Smad3L downwards, while elevating P-Smad3C and Smad4 protein expressions. Additional investigations revealed a significant reduction in α-SMA, Col-I, and Col-III levels in cell culture fluids, suggesting a decrease in collagen synthesis and a protective role against cellular damage. Western blot analyses demonstrated that the TGF-ß1/Smad pathway inhibitor, PFD, acted in synergy with YJSB, enhancing its regulatory effects on this pathway, decreasing levels of TGF-ß1, P-Smad2L, P-Smad2C, P-Smad3L, and promoting the expression of P-Smad3C. CONCLUSIONS: YJSB demonstrates a pharmacodynamic effect against HF, enhancing liver functionality and effectively mitigating the damage associated with bile duct obstruction. The proposed action mechanism of YJSB involves modulation of the TGF-ß1/Smad signaling pathway. Research indicates that YJSB might play a role in suppressing the movement, programmed cell death, and activation of HSC-T6, potentially decelerating the advancement of hepatic fibrosis.

Network pharmacology combined with experimental validation reveals the mechanism of action of Cangerzisan on allergic rhinitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Allergic rhinitis (AR) stands as a non-infectious inflammatory condition affecting the nasal mucosa, marked by bouts of sneezing, nasal itching, and congestion. This ailment afflicts individuals across all age groups and poses challenges for effective treatment due to its chronic nature. Cangerzisan (CEZS), documented in the Jishengfang compendium, represents a traditional Chinese medicinal formula long utilized for AR management. AIM OF THE STUDY: Investigating mechanism beneath therapeutic effect of CEZS in alleviating AR. MATERIALS AND METHODS: The main active components in CEZS were determined by High Performance Liquid Chromatography (HPLC).The active constituents of CEZS and their corresponding targets were identified through an exhaustive screening process employing TCMSP database. To identify targets relevant to AR, GeneCards, OMIM, and DisGeNET databases were thoroughly applied. Protein-protein interaction (PPI) network was assembled utilizing STRING platform. Potential signaling pathways influenced by CEZS were delineated through GO and KEGG enrichment analyses. Subsequently, an AR model was induced by administering aluminum hydroxide (Al(OH)3) and ovalbumin (OVA) for affecting basal and local sensitization, respectively, facilitating experimental validation of the principal signaling pathways. RESULTS: There were 61 active constituents identified within CEZS, targeting a pool of 129 entities associated with AR treatment. Pathways analysis of KEGG revealed that CEZS potentially inhibits AR advancement via modulating TLR4 signaling pathway. Animal experiments demonstrated that CEZS effectively alleviated symptom scores in guinea pigs with AR. Moreover, it exhibited notable improvements in serum immune and inflammatory factors levels, as well as reduced inflammatory infiltration within nasal mucosa, including goblet and mast cells. CEZS was found to enhance GATA-3 expression while reducing T-bet expression, thereby modulating the TH1/TH2 immune balance. Additionally, CEZS downregulated HMGB1, TLR4, and p-NF-κB/NF-κB protein expressions within nasal mucosa of guinea pigs. CONCLUSIONS: The therapeutic mechanism of CEZS against AR involves rectifying TH1/TH2 immune imbalance and upregulating inflammatory and immune factors through modulating key proteins expression within TLR4 pathway. This targeted regulation effectively impedes AR progression.

Tumor microenvironment activation amplify oxidative stress promoting tumor energy remodeling for mild photothermal therapy and cuproptosis.

Tumor metabolic reprogramming requires high levels of adenosine triphosphate (ATP) to maintain treatment resistance, which poses major challenges to chemotherapy and photothermal therapy. Especially, high levels of ATP promote copper ion efflux for limiting the curative effect of cuproptosis. Here, an H2S-responsive mesoporous Cu2Cl(OH)3-loading chemotherapeutic cisplatin (CDDP) was synthesized, and the final nanoparticle, CDDP@Cu2Cl(OH)3-CDs (CDCuCDs), was encapsulated by electrostatic action with carbon dots (CDs). CDCuCDs reacted with overproduction H2S in colon tumor to produce photothermic copper sulfide for photothermal therapy. CDDP was released by lysis to achieve chemotherapeutic effects. Importantly, CDDP elevated H2O2 levels in cells through a cascade reaction and continuously transforms H2O2 into highly cytotoxic •OH through chemodynamic therapy between H2O2 and Cu+, which enables nanoparticles to generate •OH and improve the chemotherapeutic efficacy. Highly toxic •OH disrupts mitochondrial homeostasis, prohibiting it from performing normal energy-supplying functions. Down-regulated ATP inhibits heat shock protein expression, which promotes the therapeutic effect of mild photothermal therapy and reduces the efflux of intracellular copper ions, thus improving the therapeutic effect of cuproptosis. Our research provides a potential therapeutic strategy using overproduction H2S responses in tumors, allowing tumor microenvironment-activated •OH nanogenerators to promote tumor energy remodeling for cancer treatment.

The Antioxidant Properties, Metabolism, Application and Mechanism of Ferulic Acid in Medicine, Food, Cosmetics, Livestock and Poultry.

Ferulic acid is a ubiquitous ingredient in cereals, vegetables, fruits and Chinese herbal medicines. Due to the ferulic phenolic nucleus coupled to an extended side chain, it readily forms a resonant-stable phenoxy radical, which explains its potent antioxidant potential. In addition, it also plays an important role in anti-cancer, pro-angiogenesis, anti-thrombosis, neuroprotection, food preservation, anti-aging, and improving the antioxidant performance of livestock and poultry. This review provides a comprehensive summary of the structure, mechanism of antioxidation, application status, molecular mechanism of pharmacological activity, existing problems, and application prospects of ferulic acid and its derivatives. The aim is to establish a theoretical foundation for the utilization of ferulic acid in medicine, food, cosmetics, livestock, and poultry.

A Highly Sustainable Supramolecular Bioplastic Film with Superior Hydroplasticity and Biodegradability.

Massive accumulation of postconsumer plastic waste in eco-system has raised growing environmental concerns. Sustainable end-of-life managements of the indispensable plastic are highly demanding and challenging in modern society. To relieve the plastic menace, herein we present a full life cycle sustainable supramolecular bioplastic made from biomass-derived polyelectrolyte (chitosan quaternary ammonium salt, QCS) and natural sodium fatty acid (sodium laurate, SL) through solid-phase molecular self-assembly (SPMSA), by which the QCS-SL complexes, precipitated from mixing the aqueous solutions, self-assemble to form bioplastic film by mildly pressing at room temperature. The QCS-SL bioplastic films display superior hydroplasticity owing to the water-activated molecular rearrangement and electrostatic bond reconstruction, which allows facile self-healing and reprocessing at room temperature to significantly extend the service lifetime of both products and raw materials. With higher water content, the dynamic electrostatic interactions and precipitation-dissolution equilibrium endow the QCS-SL bioplastic films with considerable solubility in water, which is promising to mitigate the plastic accumulation in aquatic environment. Because both QCS and SL are biocompatible and biodegradable, the dissolved QCS-SL films are nontoxic and environmentally friendly. Thus, this novel supramolecular bioplastic is highly sustainable throughout the whole life cycle, which is expected to open a new vista in sustainable plastic materials.

Brain responses to intermittent fasting and the healthy living diet in older adults.

Diet may promote brain health in metabolically impaired older individuals. In an 8-week randomized clinical trial involving 40 cognitively intact older adults with insulin resistance, we examined the effects of 5:2 intermittent fasting and the healthy living diet on brain health. Although intermittent fasting induced greater weight loss, the two diets had comparable effects in improving insulin signaling biomarkers in neuron-derived extracellular vesicles, decreasing the brain-age-gap estimate (reflecting the pace of biological aging of the brain) on magnetic resonance imaging, reducing brain glucose on magnetic resonance spectroscopy, and improving blood biomarkers of carbohydrate and lipid metabolism, with minimal changes in cerebrospinal fluid biomarkers for Alzheimer's disease. Intermittent fasting and healthy living improved executive function and memory, with intermittent fasting benefiting more certain cognitive measures. In exploratory analyses, sex, body mass index, and apolipoprotein E and SLC16A7 genotypes modulated diet effects. The study provides a blueprint for assessing brain effects of dietary interventions and motivates further research on intermittent fasting and continuous diets for brain health optimization. For further information, please see ClinicalTrials.gov registration: NCT02460783.

Activation of Nrf2 inhibits atherosclerosis in ApoE-/- mice through suppressing endothelial cell inflammation and lipid peroxidation.

BACKGROUND: Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, is critically involved in the regulation of oxidative stress and inflammation. However, the role of endothelial Nrf2 in atherogenesis has yet to be defined. In addition, how endothelial Nrf2 is activated and whether Nrf2 can be targeted for the prevention and treatment of atherosclerosis is not explored. METHODS: RNA-sequencing and single-cell RNA sequencing analysis of mouse atherosclerotic aortas were used to identify the differentially expressed genes. In vivo endothelial cell (EC)-specific activation of Nrf2 was achieved by injecting adeno-associated viruses into ApoE-/- mice, while EC-specific knockdown of Nrf2 was generated in Cdh5CreCas9floxed-stopApoE-/- mice. RESULTS: Endothelial inflammation appeared as early as on day 3 after feeding of a high cholesterol diet (HCD) in ApoE-/- mice, as reflected by mRNA levels, immunostaining and global mRNA profiling, while the immunosignal of the end-product of lipid peroxidation (LPO), 4-hydroxynonenal (4-HNE), started to increase on day 10. TNF-α, 4-HNE, and erastin (LPO inducer), activated Nrf2 signaling in human ECs by increasing the mRNA and protein expression of Nrf2 target genes. Knockdown of endothelial Nrf2 resulted in augmented endothelial inflammation and LPO, and accelerated atherosclerosis in Cdh5CreCas9floxed-stopApoE-/- mice. By contrast, both EC-specific and pharmacological activation of Nrf2 inhibited endothelial inflammation, LPO, and atherogenesis. CONCLUSIONS: Upon HCD feeding in ApoE-/- mice, endothelial inflammation is an earliest event, followed by the appearance of LPO. EC-specific activation of Nrf2 inhibits atherosclerosis while EC-specific knockdown of Nrf2 results in the opposite effect. Pharmacological activators of endothelial Nrf2 may represent a novel therapeutic strategy for the treatment of atherosclerosis.

Synergistic effect of modified anhydrous magnesium carbonate and hexaphenoxycyclotriphosphazene on flame retardancy of ethylene-vinyl acetate copolymer.

Ethylene-vinyl acetate copolymer (EVA) is widely used in various applications; however, its flammability limits its application in wire and cable industries. In this study, 3-methacryloxypropyltrimethoxysilane (KH570) was successfully grafted onto the surface of anhydrous magnesium carbonate (AMC) by alkali activation treatment. The KH570 modified AMC (AMC@KH570) was then introduced into the EVA matrix along with hexaphenoxycyclotriphosphazene (HPCTP) to assess their effects on the flame retardancy and mechanical properties of EVA composites. The results illustrate a significant synergistic effect in enhancing the flame retardancy of EVA composites by using AMC@KH570 and HPCTP, and the limiting oxygen index (LOI) and vertical burning test (UL-94) of EVA filled with 5 wt% HPCTP and 45 wt% AMC@KH570 (mAMC/H-45-5) reached 27.6% and V-0, respectively. The flame retardant mechanism was investigated by thermogravimetric/infrared (TG-IR) spectroscopy and residual carbon composition analysis. The results show that the thermal decomposition of AMC@KH570 and HPCTP consists of gas dilution, free radical quenching, and catalytic carbonization. Furthermore, KH570 works as a bridge to improve the compatibility of AMC and EVA matrix, which offsets the mechanical loss of EVA to some extent. The present research provides a new path to modify AMC and fabricate EVA composites with excellent flame retardant properties.

Inventorization and ecological risk assessment of tetrabromobisphenol A and hexabromocyclododecane in sediments from Guangdong coastal area of South China Sea.

Brominated flame retardants (BFRs) exhibit excellent flame retardant properties and are widely used in various industries. Among the common BFRs, tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCDs) pose substantial ecological and human health risks due to their extensive application and long-range transport. This study established 131 sample collection sites along the coast of the South China Sea (SCS) in Guangdong Province to assess the concentration, distribution, inventory, and ecological risk of TBBPA and HBCDs in surface sediments. The concentrations of TBBPA in SCS sediments ranged from < limit of detection (LOD) to 80 µg/kg dry weight (dw), and those of HBCDs from < LOD to 18 µg/kg dw. The diastereoisomers of HBCDs (α-, ß-, and γ-HBCD) in the sediment samples accounted for 36 %, 13 %, and 51 %, respectively. Human activities, particularly those associated with nearby electronic waste disassembly and textile and garment industries, considerably influenced the dispersion of TBBPA and HBCDs. The inventories of TBBPA and HBCDs in Guangdong Province's SCS were estimated to be 3.2 × 105 kg and 7.2 × 104 kg, respectively. The average risk quotient values ranged from <0.01 to 0.016, indicating a low to negligible environmental risk. This study provides deeper insights into the distribution and scientific significance of HBCDs and TBBPA in SCS sediment samples, elucidates the current state of BFR contamination, and offers recommendations for future research on environmental safety and human health in the region.

Recyclable and elastic highly thermally conductive epoxy-based composites with covalent-noncovalent interpenetrating networks.

High-power electronic architectures and devices require elastic thermally conductive materials. The use of epoxy resin in thermal management is limited due to its rigidity. Here, based on epoxy vitrimer, flexible polyethylene glycol (PEG) chains are introduced into covalent adaptable networks to construct covalent-noncovalent interpenetrating networks, enabling the elasticity of epoxy resins. Compared to traditional silicone-based thermal interface materials, the newly developed elastic epoxy resin shows the advantages of reprocessability, self-healing, and no small molecule release. Results show that, even after being filled with boron nitride and liquid metal, the material maintains its resilience, reprocessability and self-healing properties. Leveraging these characteristics, the composite can be further processed into thin films through a repeated pressing-rolling technique that facilitates the forced orientation of the fillers. Subsequently, the bulk composites are reconstructed using a film-stacking method. The results indicate that the thermal conductivity of the reconstructed bulk composite reaches 3.66 W m-1 K-1, achieving a 68% increase compared to the composite prepared through blending. Due to the existence of covalent adaptable networks, the inorganic and inorganic components of the composite prepared in this work can be completely separated under mild conditions, realizing closed-loop recycling.

Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

Chlorella filled poly(lactic acid) (PLA)/poly(butylene adipate-co-terephthalate) (PBAT) blend bio-composites compatible with additive manufacturing processes: Fluorescent and anti-counterfeiting QR codes applications.

Anti-counterfeiting in 3D printing has gained significant attention, however, current approaches often fall short of fully capitalizing on the inherent advantages of personalized manufacturing with this technology. Herein, we propose an embedded anti-counterfeiting scheme for additive manufacturing, accompanied by a novel fluorescent encrypted quick response (QR) method. This approach involves the development of a 3D printing filament utilizing poly(lactic acid) (PLA) and poly(butylene adipate-co-terephthalate) (PBAT) bio-composites as the primary filament matrix, with varying quantities of Chlorella powder incorporated. The resulting filament has a good thermal stability near 200 °C and exhibits a distinctive red fluorescence under ultraviolet light, with the emission peak at 677 nm when excited by 415 nm blue light. Fluorescence imaging analysis confirms that the red fluorescence in 3D printed devices containing Chlorella is a result of the chlorophyll and its derivatives fluorescence effect. The fluorescent encrypted QR codes are inconspicuous in daylight but become easily discernible under ultraviolet light. In the cases of recognizable QR codes, the ∆Eab* values all exceed 35, and the LC/LB values deviate significantly from 1. This research delves into the fluorescence characteristics of Chlorella and highlights its applicability in 3D printing, specifically within the realm of product anti-counterfeiting, presenting a groundbreaking approach.

Pien Tze Huang (PZH) protects endothelial function in diabetic mice.

Endothelial dysfunction is the most common pathological feature of cardiovascular diseases, including diabetes mellitus, hypertension and atherosclerosis. It affects both macro- and micro-vasculatures, causing functional impairment of multiple organs. Pien Tze Huang (PZH) is a well-studied traditional Chinese medicine (TCM) with multiple pharmacological properties that produces therapeutic benefits against colorectal cancer, non-alcoholic steatohepatitis and neurodegenerative diseases. However, it is unknown how PZH affects vascular function under pathological conditions. Therefore, this study aimed to investigate the effect of PZH on endothelial function and the underlying mechanisms in db/db diabetic mice. The results showed that chronic treatment of PZH (250 mg/kg/day, 5 weeks) improved endothelial function by restoring endothelium-dependent relaxation through the activation of the Akt-eNOS pathway and inhibition of endothelial oxidative stress, which increased nitric oxide bioavailability. Furthermore, PZH treatment increased insulin sensitivity and suppressed inflammation in diabetic mice. These new findings suggest that PZH may have vaso-protective properties and the potential to protect against diabetic vasculopathy by preserving endothelial function.

H2S-driven chemotherapy and mild photothermal therapy induced mitochondrial reprogramming to promote cuproptosis.

The elevated level of hydrogen sulfide (H2S) in colon cancer hinders complete cure with a single therapy. However, excessive H2S also offers a treatment target. A multifunctional cascade bioreactor based on the H2S-responsive mesoporous Cu2Cl(OH)3-loaded hypoxic prodrug tirapazamine (TPZ), in which the outer layer was coated with hyaluronic acid (HA) to form TPZ@Cu2Cl(OH)3-HA (TCuH) nanoparticles (NPs), demonstrated a synergistic antitumor effect through combining the H2S-driven cuproptosis and mild photothermal therapy. The HA coating endowed the NPs with targeting delivery to enhance drug accumulation in the tumor tissue. The presence of both the high level of H2S and the near-infrared II (NIR II) irradiation achieved the in situ generation of photothermic agent copper sulfide (Cu9S8) from the TCuH, followed with the release of TPZ. The depletion of H2S stimulated consumption of oxygen, resulting in hypoxic state and mitochondrial reprogramming. The hypoxic state activated prodrug TPZ to activated TPZ (TPZ-ed) for chemotherapy in turn. Furthermore, the exacerbated hypoxia inhibited the synthesis of adenosine triphosphate, decreasing expression of heat shock proteins and subsequently improving the photothermal therapy. The enriched Cu2+ induced not only cuproptosis by promoting lipoacylated dihydrolipoamide S-acetyltransferase (DLAT) heteromerization but also performed chemodynamic therapy though catalyzing H2O2 to produce highly toxic hydroxyl radicals ·OH. Therefore, the nanoparticles TCuH offer a versatile platform to exert copper-related synergistic antitumor therapy.

SLA-3d printed building and characteristics of GelMA/HAP biomaterials with gradient porous structure.

Developing a gradient porous scaffold similar to bone structure is gaining increasing attention in bone tissue engineering. The GelMA/HAP hydrogel has demonstrated potential in bone repair. Although 3D printing can build GelMA/HAP with porous structure, fabricating porous GelMA/HAP with gradient porosity and pore size in one step remains challenging. In this paper, a gradient porous structure with controllable pore size, based on gelatin methacryloyl (GelMA) and hydxroxyapatite (HAP), was engineered and printed using stereolithography. Firstly, the GelMA and HAP were mixed to prepare a hydrogel with a solid content ranging from 10 wt% to 50 wt% for stereolithography. Taking advantage of the sol-gel characteristics of GelMA/HAP hydrogel, GelMA/HAP was fed on the workbench through a combination of extrusion and paving to form a thin layer. During the curing of each layer, the hydrogel exposed to the curing of a single UV beam immediately solidified, forming a highly interconnected porous structure. Additionally, the hydrogel outside the scanning range could be further polymerized to form a relatively dense structure due to the residual laser energy. Finally, without gradient structural design or changing printing parameters, the gradient porous structure of bone-like could be printed in a single-step process. By adjusting the curing parameters of the single UV beam and the concentration and size of ceramic in the hydrogel, the printed pore diameter of the spongy structure could be controlled within the range of 50-260 µm, while the thickness of the compact area could be adjusted within 130-670 µm.

Effects of selective serotonin reuptake inhibitors (SSRIs) on suicide: A network meta-analysis of double-blind randomized trials.

The relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and suicide risk in patients with mental disorders remains controversial. We conducted a network meta-analysis to examine the effects of SSRIs on suicide risk in patients with mental disorders. A comprehensive search was conducted across PubMed, Web of Science, PsycINFO, CENTRAL, Wanfang Database, and China National Knowledge Infrastructure for articles published until December 19, 2023. The main outcomes were suicidal ideation and instances of suicidal behavior. We included 29 double-blind randomized trials in our analysis. The findings suggest that SSRIs primarily offer short-term protection against suicidal ideation. By week 2, paroxetine, fluoxetine, escitalopram, and non-SSRI treatments were linked to a decreased suicide risk compared with a placebo, with the exception of sertraline. This protective effect was diminished by week 8. In contrast, studies on instances of suicidal behavior from weeks 1 to 10 found no significant difference in efficacy between SSRIs, non-SSRIs, and placebo. These results indicate that SSRIs may offer short-term protection against suicidal ideation. However, their long-term effectiveness in mitigating suicidal ideation and preventing suicidal behaviors is limited.

Surveillance for adverse events following immunization with DTaP-containing combination vaccines in Linping, China, 2019-2022.

Background: The DTaP-Hib and DTaP-IPV/Hib combination vaccine can be used as a substitute for the diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). We aimed to evaluate the safety of multi-component vaccines containing DTaP by analyzing the reporting rates and characteristics of adverse events following immunization (AEFIs) in Linping District during the years 2019 to 2022. Methods: We obtained data of AEFI and vaccination from the National AEFI Surveillance System of China and Zhejiang Municipal Immunization Information Management System, respectively, during 2019-2022 for a descriptive, epidemiological analysis. Results: The total number of AEFI reported following vaccinations with DTaP-containing combination vaccines was 802 in Linping District from 2019 to 2022. The overall reporting rates of AEFIs following DTaP, DTaP-Hib, and DTaP-IPV/Hib vaccinations were 445.72 (537 cases), 536.29 (45 cases), and 306.13 (220 cases) per 100,000 doses in Linping District from 2019 to 2022, respectively. Only one case of a serious AEFI following DTaP vaccination, with a reporting rate of 0.83 per 100,000 doses. The composition ratio of vaccine product-related reactions for DTaP, DTaP-Hib, and DTaP-IPV/Hib were 99.81, 97.78, and 100.00%, respectively. The composition ratio of coincidental events for DTaP and DTaP-Hib were 0.19 and 2.22%, respectively. The reporting rates of total AEFIs for DTaP-IPV/Hib were lower than for DTaP. The reporting rate of local induration for DTaP-Hib was lower than for DTaP, and the reporting rates of local redness & swelling and local induration for DTaP-IPV/Hib were both lower than for DTaP. DTaP-IPV/Hib had a higher proportion of AEFIs in first quarter compared to DTaP. The reporting rate after the second dose of DTaP-Hib was higher than that of DTaP, and the reporting rates of AEFIs after the first dose and third dose of DTaP-IPV/Hib were lower than DTaP. Conclusion: The reported AEFIs to multi-component vaccines containing DTaP components during 2019-2022 in Linping District were mainly mild vaccine reactions. DTaP-containing combination vaccines demonstrated a good safety profile.

A peptide selectively recognizes Gram-negative bacteria and forms a bacterial extracellular trap (BET) through interfacial self-assembly.

An innate immune system intricately leverages unique mechanisms to inhibit colonization of external invasive Bacteria, for example human defensin-6, through responsive encapsulation of bacteria. Infection and accompanying antibiotic resistance stemming from Gram-negative bacteria aggregation represent an emerging public health crisis, which calls for research into novel anti-bacterial therapeutics. Herein, inspired by naturally found host-defense peptides, we design a defensin-like peptide ligand, bacteria extracellular trap (BET) peptide, with modular design composed of targeting, assembly, and hydrophobic motifs with an aggregation-induced emission feature. The ligand specifically recognizes Gram-negative bacteria via targeting cell wall conserved lipopolysaccharides (LPS) and transforms from nanoparticles to nanofibrous networks in situ to trap bacteria and induce aggregation. Importantly, treatment of the BET peptide was found to have an antibacterial effect on the Pseudomonas aeruginosa strain, which is comparable to neomycin. Animal studies further demonstrate its ability to trigger aggregation of bacteria in vivo. This biomimetic self-assembling BET peptide provides a novel approach to fight against pathogenic Gram-negative bacteria.

A Hydrogel Electrolyte with High Adaptability over a Wide Temperature Range and Mechanical Stress for Long-Life Flexible Zinc-Ion Batteries.

Flexible zinc-ion batteries have garnered significant attention in the realm of wearable technology. However, the instability of hydrogel electrolytes in a wide-temperature range and uncontrollable side reactions of the Zn electrode have become the main problems for practical applications. Herein, N,N-dimethylformamide (DMF) to design a binary solvent (H2O-DMF) is introduced and combined it with polyacrylamide (PAM) and ZnSO4 to synthesize a hydrogel electrolyte (denoted as PZD). The synergistic effect of DMF and PAM not only guides Zn2+ deposition on Zn(002) crystal plane and isolates H2O from the Zn anode, but also breaks the hydrogen bonding network between water to improve the wide-temperature range stability of hydrogel electrolytes. Consequently, the symmetric cell utilizing PZD can stably cycle over 5600 h at 0.5 mA cm- 2@0.5 mAh cm-2. Furthermore, the Zn//PZD//MnO2 full cell exhibits favorable wide-temperature range adaptability (for 16000 cycles at 3 A g-1 under 25 °C, 750 cycles with 98 mAh g-1 at 0.1 A g-1 under -20 °C) and outstanding mechanical properties (for lighting up the LEDs under conditions of pressure, bending, cutting, and puncture). This work proposes a useful modification for designing a high-performance hydrogel electrolyte, which provides a reference for investigating the practical flexible aqueous batteries.