Molecular cloning and functional characterization of eight galectin genes from Takifugu obscurus.

Galectins are a family of animal lectins involved in the immune response against pathogens. However, the roles of fish galectins during pathogen infection require comprehensive studies. In the present research, eight different galectin genes from Takifugu obscurus (named ToGalec1-8) were identified and characterized. ToGalec1-8 encoded proteins of 240, 182, 373, 145, 452, 135, 359 and 346 amino acids, respectively. All predicted ToGalec1-8 proteins possessed one or more conserved carbohydrate recognition domains (CRDs). Phylogenetic analysis revealed that ToGalec1-8 were evolutionarily closely related to their counterparts in other selected vertebrates, hinting their genetic relationship. Tissue distribution analysis showed that most ToGalec genes were distributed ubiquitously in all detected tissues, with relatively high expression in immune tissues. After stimulation by Vibrio harveyi and Staphylococcus aureus, the mRNA transcripts of ToGalec1-8 in liver and kidney were significantly upregulated. In addition, RNA interference experiments indicated that knockdown of ToGalec1 and ToGalec7 inhibited the clearance of bacteria in vivo. Taken together, these obtained results suggested that ToGalec1-8 play an important role in innate immunity and defense against bacterial infection in T. obscurus.

Prevalence of antibiotic resistance genes, heavy metal, and bacterial community composition in sea sediments influenced by Eriocheir sinensis breeding aquaculture.

Eriocheir sinensis is the main aquaculture species in China. With the continuous expansion of the aquaculture scale, the demand for E. sinensis seedlings was also increased. The water used in breeding has well-nourished and its discharge into the sea posed significant risks. This study sampled the wastewater discharge points of the E. sinensis seedlings in Sheyang County, Jiangsu Province, and the areas far from the discharge points that were not affected in March and May 2023, respectively. A large number of antibiotic resistance genes (ARGs) were found in the sediment of the wastewater discharge area, and the highest ARG was sulfonamide ARG-sul1 using qPCR analysis, while ARGs were almost undetectable in the areas not affected by wastewater discharge. The 16S rRNA sequence analysis results showed that the main bacterial phyla at the wastewater discharge point were Bacteroidetes, Proteobacteria, and Thermodesulfobacteria. In the control point, the main bacterial phyla were Proteobacteria, Chlorobacterium, and Thermodesulfobacteria. There were significant differences in the composition of microbial communities between the two points, and the samples at the wastewater discharge point were more clustered and had higher similarity. The correlation network and redundancy analysis indicated that the phyla Bacteroidetes, Firmicutes, and Proteobacteria at the wastewater discharge points were positively correlated with most ARGs. The wastewater discharge had no effect on heavy metals from the two points. This study sets a foundation for future research by identifying key microbial taxa as potential ARG carriers and examining the interactions between microbial communities, ARGs, and heavy metals.

Correlation analysis of serum Rac1 level with asthma control, airway inflammatory response and lung function in asthmatic children.

OBJECTIVE: To investigate the correlation between serum Rac1 enzyme (Rac1) level with asthma control, airway inflammatory response and lung function in asthmatic children. METHODS: A retrospective analysis was performed on 79 children with asthma who were diagnosed and treated in our hospital from June 2020 to January 2023. According to the severity of the disease, the children were divided into mild group (25 cases), moderate group (30 cases) and severe group (24 cases). 36 healthy children who underwent physical examination at the same period in our hospital were selected as the control group. The state of an illness, control level, serum mRNA Rac1, inflammatory factors, and lung function of the children in two groups were compared between the control group and the observation group. RESULTS: The Rac1 mRNA levels, forced vital capacity (FVC), forced expiratory volume in one second/FVC (FEV1/FVC), peak expiratory flow (PEF), and maximum mid-expiratory flow (MMEF) in the observation group were significantly lower than these in the control group (P < 0.05). The tumor necrosis factor-alpha (TNF-α), interleukin-5 (IL-5), IL-6, and IL-33 in the observation group were markedly higher than these in the control group (P < 0.05). As the state of an illness worsened, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually reduced (P < 0.05), while the levels of TNF-α, IL-5, IL-6, and IL-33 increased (P < 0.05). As the degree of disease control improved, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually elevated (P < 0.05), and the levels of TNF- α, IL-5, IL-6, and IL-33 showed the opposite trend (P < 0.05). Rac1 was negatively related to the levels of TNF-α, IL-5, IL-6 and IL-33 (P < 0.05), and positively to the levels of FVC, FEV1/FVC, PEF and MMEF (P < 0.001). Rac1 mRNA levels, FVC, FEV1/FVC, PEF and MMEF were protective factors, while TNF-α, IL-5, IL-6 and IL-33 were risk factors for the prognosis of children with asthma (P < 0.05). CONCLUSION: Children with asthma have obviously lower serum Rac1 mRNA levels, higher inflammatory factor levels and lower lung function. Serum Rac1 mRNA level may be associated with better asthma control, lower airway inflammatory response, better lung function and lower disease severity. It has important reference value for the evaluation of the state of an illness, efficacy and prognosis of children with bronchial asthma.

Unraveling the Fluoride-Induced Interface Reconstruction Across Lead-Based Hierarchical MnO2 Anode in Zinc Electrowinning.

Although the hierarchical manganese dioxide film electrode shows promise as a durable and catalytically active anode for zinc electrowinning, it often fails and deactivates when it is exposed to fluoride-rich environments. The lack of understanding regarding the mechanism behind fluoride-induced irreversible interface reconstruction hinders their practical application in large-scale energy-saving and pollution-reduction efforts. Here, we conducted multidimensional operando investigations to gain insights into the dynamic evolution across the film electrode interface with temporal and spatial resolution. Our findings reveal that electroosmosis of F- initially triggers structural collapse and subsequent reconstruction of [MnO6] units, followed by interaction with the spontaneous oxide film at the surface of lead substrate. Experimental studies and theoretical calculations indicate that F- facilitates the irreversible transformation of γ-MnO2 into more stable yet protective catalytic dual-defective α-MnO2. Additionally, lower levels of F- at the interface promote a change in microenvironmental pH within porous PbSO4, triggering the development of microporous corrosion-resistant ß-PbO2 as the dominant phase. The combined effects of MnO2 and interphase evolution effectively explain the abnormally elevated oxygen evolution overpotential. Then, the proposed appropriate application scenarios based on the corrosion behavior will serve as a practical guide for the implementation of the hierarchical manganese dioxide film electrode.

Botany, phytochemistry, pharmacologic activities, traditional applications, pharmacokinetics, quality control and toxicity of Zanthoxyli Radix: An updated review.

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxyli Radix (ZR), the dry root of Zanthoxylum nitidum (Roxb.) DC (ZN) is known as Liang Mian Zhen in China and has been the preferred Chinese medicine for the treatment of inflammation and cancer disease at home and abroad. ZR has been used as the core ingredient in anti-inflammatory traditional medicines, such as Sanjiuweitai granules and Jinji tablets, etc. AIM OF THE WORK: This review aimed to provide a comprehensive overview of ZR in terms of traditional uses, quality control, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics. Meanwhile, the anti-inflammatory substances and mechanism of ZR were emphasized, to offer new perspectives and broad scopes for future studies. MATERIALS AND METHODS: The information was retrieved from Web of Science, Researchgate, Google Scholar, SciFinder, X-MOL, PubMed, China National Knowledge Infrastructure (CNKI), Chinese Masters and Doctoral Dissertations, and Elsevier between 1984 and 2024. RESULTS: Till now, a total of 184 chemical components have been identified in ZR, including 91 alkaloids, 22 lignans, 4 flavonoids, 19 coumarins, 17 terpenoids, and 31 other types. Pharmacological studies have proved that ZR had a variety of biological activities, such as anti-tumour, antibacterial, antioxidant and other activities, particularly in anti-inflammation. ZR exerts anti-inflammatory disease effects by modulating various signaling pathways, including MAPK, NF-κB, P13/AKT and JAK/STAT. Pharmacokinetic studies have shown that ZR exhibits low absorption rates, broad distribution, and rapid metabolism. Additionally, this review also revealed the shortcomings of current research on ZR and possible future research directions. CONCLUSION: Extensive literature analysis indicates that ZR and its bioactive constituents possess diverse pharmacological activities, especially anti-inflammation. Moreover, in order to promote the safety and adaptability of ZR in clinical application, it is also strongly recommended that further research should focus on toxicity studies, pharmacokinetic studies of herb-drug interactions, and quality control.

Sophorae tonkinensis radix et rhizoma: A comprehensive review of the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, toxicology and detoxification strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR), the dried root and rhizome of Sophora tonkinensis Gagnep., is commonly used in the treatment of tonsillitis and pharyngitis, throat soreness and throat obstruction, swelling and aching of gum, etc. in China or other Asian countries. STR is usually used as the core herb in traditional Chinese medicine preparations, such as "Biyanling Tablets", "Fufang Muji Granules" and "Ganyanling Injections", etc. AIM OF THE REVIEW: This review aimed to provide a comprehensive analysis of STR in terms of botany, traditional use, phytochemistry, ethnopharmacology, pharmacology, pharmacokinetics, toxicology and detoxification strategy, to provide a rational application in future research. MATERIALS AND METHODS: The information involved in the study was gathered from a variety of electronic resources, including China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations. RESULTS: Till now, a total of 333 chemical components have been identified in STR, including 85 alkaloids, 124 flavonoids, 24 triterpenes, 27 triterpene saponins, 34 organic acids, 8 polysaccharides, etc. STR and its main active constituents have cardiovascular protection, anti-tumor activity, anti-inflammatory activity, antipyretic activity, analgesic activity, antibacterial activity, antifungal activity, antiviral activity, and hepatoprotective activity, etc. However, toxic effects of STR on the liver, nerves, heart, and gastrointestinal tract have also been observed. To mitigate these risks, STR needs attenuation before use, with the most common detoxification methods being processing and combined use with other drugs. The pharmacokinetics of STR in vivo and traditional and clinical prescriptions containing STR have been sorted out. Despite the potential therapeutic benefits of STR, further research is warranted to elucidate its hepatotoxicity, particularly in vivo, exploring aspects such as in vivo metabolism, distribution, and mechanisms. CONCLUSION: This review serves to emphasize the therapeutic potential of STR and highlights the crucial need to address its toxicity concerns before considering clinical application. Further research is required to comprehensively investigate the toxicological properties of STR, with particular emphasis on its hepatotoxicity and neurotoxicity. Such research endeavors have the potential to standardize the rational application of STR for optimal therapeutic outcomes.

Epidemiological trends in respiratory pathogens infections among children post-COVID-19: A cross-sectional study.

Objective: The aim of this study was to investigate the epidemiological trend of respiratory pathogens infections among children after the Coronavirus Disease 2019 (COVID-19) pandemic. Methods: This study enrolled 575,373 children who came to our hospital for relevant respiratory pathogen antigen/antibody testing due to respiratory symptoms such as fever and cough. The demographic and laboratory data, including age, gender, testing time, and influenza A virus (IAV), influenza B virus (IBV), respiratory syncytial virus (RSV), adenovirus (ADV), and Mycoplasma pneumonia (MP) results, were collected from electronic medical records. SPSS (version 21.0) and GraphPad Prism 9 software were used for statistical analysis and figure creation. Results: 79,746 children tested positive for IAV IgM, and 3196 children tested positive for IBV IgM, with an overall positive rate of 28.5 % for IAV and 1.1 % for IBV. IAV infections peaked at 21,502 cases in March 2023. 80,699 children underwent RSV IgM testing from April to October 2023, with 5726 (7.1 %) testing positive. The apex of RSV infections occurred in May 2023, with 2140 cases. Regarding ADV, 100,460 children underwent testing from April to October 2023, with 1981 (11.9 %) testing positive. The pinnacle of ADV infections reached 4546 cases in November 2023. Concerning MP, 474,913 children underwent MP testing, with 73,833 (15.5 %) testing positive. The zenith of MP infections occurred in November 2023, with 25,291 cases. Further analysis revealed that the outbreaks of these pathogens are occurring earlier than in previous years. Additionally, our data showed that children aged >3 years accounted for 79.6 %, 87.8 %, 88.6 %, and 77.8 % of the total IAV-positive, IBV-positive, ADV-positive, and MP-positive children, respectively. Conversely, RSV primarily infected children <6 years. Conclusion: Various respiratory pathogens showed an epidemic trend in children among children post-COVID-19. These results indicated that we should pay timely attention to the epidemiological trends and characteristics of respiratory pathogens in children after the COVID-19 pandemic and provide relevant information for society and clinical practice.

Activation of α7 nicotinic acetylcholine receptors inhibits hepatic necroptosis and ameliorates acute liver injury in mice.

BACKGROUND: Acute liver injury (ALI) is a disease characterized by severe liver dysfunction, caused by significant infiltration of immune cells and extensive cell death with a high mortality. Previous studies demonstrated that the α7 nicotinic acetylcholine receptor (α7nAChR) played a crucial role in various liver diseases. The hypothesis of this study was that activating α7nAChR could alleviate ALI and investigate its possible mechanisms. METHODS: ALI was induced by intraperitoneal injection of lipopolysaccharide (LPS)/D-galactosamine (D-Gal) in wild type (WT), α7nAChR knockout (α7nAChR -/-) and Sting mutation (Stinggt/gt) mice in the presence or absence of a pharmacological selective α7nAChR agonist (PNU-282987). The effects of α7nAChR on hepatic injury, inflammatory response, mitochondrial damage, necroptosis and infiltration of immune cells during ALI were assessed. RESULTS: The expression of α7nAChR in liver tissue was increased in LPS/D-Gal induced ALI mice. Compared to the age-matched WT mice, α7nAChR deficiency decreased the survival rate, exacerbated the hepatic injury accompanied with enhanced inflammatory response and oxidative stress, and aggravated hepatic mitochondrial damage and necroptosis. Conversely, pharmacological activation of α7nAChR by PNU-282987 displayed the opposite trends. Furthermore, PNU-282987 significantly reduced the proportion of infiltrating monocyte-derived macrophages (CD45+CD11bhiF4/80int), M1 macrophages (CD45+CD11b+F4/80+CD86 hiCD163low), Ly6Chi monocytes (CD45+CD11b+MHCⅡ lowLy6C hi), but increased the resident Kupffer cells (CD45+CD11bintF4/80 hiTIM4 hi) in the damaged hepatic tissues caused by LPS/D-Gal. Interestingly, α7nAChR deficiency promoted the STING signaling pathway under LPS/D-Gal stimulation, while PNU-282987 treatment significantly prevented its activation. Finally, it was found that Sting mutation abolished the protective effects against hepatic injury by activating α7nAChR. CONCLUSIONS: Our study revealed that activating α7nAChR could protect against LPS/D-Gal induced ALI by inhibiting hepatic inflammation and necroptosis possibly via regulating immune cells infiltration and inhibiting STING signaling pathway.

Coordination-driven in-situ controlled synthesis of cellulose-based fluorescent composite with tunable color for decoration, anti-counterfeiting, and accurate color recognition.

Fluorescent composites have widespread applications in many aspects. Wood-derived cellulose is a renewable, easily processed and biodegradable, and cellulose-based fluorescent composites are highly favored for in different fields. However, the existing cellulose-based fluorescent composites still have many urgent problems to be solved, such as unstable luminescence properties and easy shedding of luminescent substances, and the development of their practical applications is still a formidable challenge. Herein, a green and mild strategy for the in-situ controllable synthesis of cellulose-based fluorescent composites membrane (CFM) was developed. Firstly, delignified wood (DW) was modified with citric acid, and then lanthanide ions were introduced on modified DW through coordinated covalent bonds. Additionally, the luminescence mechanism of CFM is proposed. CFMs show adjustable color for decorative and light conversion and can be accurately identified for data protection, which increases the high value-added of cellulose-based composites. The stable luminescent properties were maintained after sonication for 30 min or solvent immersion for three months. Therefore, this work presents a new approach for the synthesis of CFM, which provides an environment-friendly strategy for manufacturing cellulose-based fluorescent materials, which is significant for the subsequent development of environment-friendly composites for anti-counterfeiting and decorative applications.

Electrochemical Reduction of CO2 into Syngas by N-Modified NiSb Nanowires.

Carbon dioxide reduction reaction (CO2RR) provides a promising method for syngas synthesis. However, it is challenging to balance the CO2RR activity and hydrogen (H2)/carbon monoxide (CO) ratios due to the limited mass transport and inefficient catalytic interface. Herein, we adopt a nitrogen (N)-modification method to synthesize N-modified nickel antimony nanowires (N-NiSb NWs/C), which are efficient for producing syngas with controllable H2/CO ratios. Significantly, the optimized N-NiSb NWs/C, with boosted electrochemical CO2RR activity, have the flexibility to control H2/CO ratios in syngas from nearly 1 to 4 in a wide potential range. The mechanistic discussion shows that the electronic structure of NiSb NWs/C can be optimized by using the synergistic effect between Ni and Sb, as well as the reasonable surface modification, so that a controllable syngas can be obtained. Our design provides an ideal platform for generating syngas with widely controllable H2/CO ratios.

Photocatalytic Overall Water Splitting with a Solar-to-Hydrogen Conversion Efficiency Exceeding 2% through Halide Perovskite.

Photocatalytic water splitting using semiconductors is a promising approach for converting solar energy to clean energy. However, challenges such as sluggish water oxidation kinetics and limited light absorption of photocatalyst cause low solar-to-hydrogen conversion efficiency (STH). Herein, we develop a photocatalytic overall water splitting system using I3-/I- as the shuttle redox couple to bridge the H2-producing half-reaction with the O2-producing half-reaction. The system uses the halide perovskite of benzylammonium lead iodide (PMA2PbI4, PMA = C6H5CH2NH2) loaded with MoS2 (PMA2PbI4/MoS2) as the H2 evolution photocatalyst, and the RuOx-loaded WO3 (WO3/RuOx) as the O2 evolution photocatalyst, achieving a H2/O2 production in stoichiometric ratio with an excellent STH of 2.07%. This work provides a detour route for photocatalytic water splitting with the help of I3-/I- shuttle redox couple in the halide perovskite HI splitting system and enlightens one to integrate and utilize multi catalytic strategies for solar-driven water splitting.

ß-cell dedifferentiation in HOMA-ßlow and HOMA-ßhigh subjects.

CONTEXT: ß-cell dedifferentiation ratio is increased in type 2 diabetes; but its direct link to in vivo ß-cell function in human remains unclear. OBJECTIVE: The present study was designed to investigate whether ß-cell dedifferentiation in situ was closely associated with ß-cell function in vivo and to identify targets crucial for ß-cell dedifferentiation/function in human. METHODS: We acquired HOMA-ß values, calculated the number of hormone-negative endocrine cells and evaluated important markers and novel candidates for ß-cell dedifferentiation/function on paraneoplastic pancreatic tissues from 13 patients with benign pancreatic cystic neoplasm (PCN) or intrapancreatic accessory spleen. RESULTS: Both ß-cell dedifferentiation ratio and dedifferentiation marker (Aldh1a3) were inversely related with in vivo ß-cell function (HOMA-ß) and in situ ß-cell functional markers Glut2 and Ucn3 in human. Moreover, the islets from HOMA-ßlow subjects were manifested as 1) increased ß-cell dedifferentiation ratio, 2) enriched dedifferentiation maker Aldh1a3, and 3) lower expression of Glut2 and Ucn3, compared to those from HOMA-ßhigh subjects. We found that basic leucine zipper transcription factor 2 (Bach2) expression was significantly induced in islets from HOMA-ßlow patients and was positively correlated with the ratio of ß-cell dedifferentiation in human. CONCLUSIONS: Our findings emphasize the contribution of ß-cell dedifferentiation to ß-cell dysfunction in human. The Bach2 induction in ß-cells with higher frequency of dedifferentiation observed in HOMA-ßlow subjects reinforce its distinctive role as a pharmaceutical target of ß-cell dedifferentiation for the treatment of human diabetes.

Association of Thallium Exposure with Decreased Renal Function among Chinese Adults - China, 2017-2018.

What is already known about this topic?: Thallium (Tl) is significantly more toxic than heavy metals such as lead, cadmium, and mercury. However, previous studies examining the relationship between Tl exposure and the risk of chronic kidney disease (CKD) have yielded inconsistent results. What is added by this report?: The study demonstrated that elevated urinary Tl levels were associated with a higher prevalence of CKD and a reduced estimated glomerular filtration rate (eGFR), particularly among older adults. These findings were consistent in the restricted cubic spline (RCS) analyses. What are the implications for public health practice?: This study identified Tl as a risk factor for decreased renal function, underscoring the need to enhance surveillance of Tl to mitigate the disease burden of CKD.

Blood mercury mediates the associations between fish consumption and serum uric acid levels among Chinese adults: A nationally representative study.

Fish consumption can increase purine load in human body, and the enrichment of mercury in fish may affect the glomerular filtration function, both resulting in increased serum uric acid (SUA) levels. The data of blood mercury (BHg), fish consumption frequency and SUA levels of 7653 participants aged 18 years or older was from China National Human Biomonitoring (2017-2018). The associations between fish consumption frequency, ln-transformed BHg and SUA levels were explored through weighted multiple linear regressions. The mediating effect of BHg levels between fish consumption frequency and SUA levels was evaluated by mediation analysis. We found that both the fish consumption frequency and BHg were positively associated with SUA levels in both sexes. Compared to participants who had never consumed fish, participants who consumed fish once a week or more had higher SUA levels [ß (95% confidence interval, CI): 20.39 (2.16, 38.62) in males; ß (95% CI): 10.06 (0.76, 19.37) in females] and ln-transformed BHg [ß (95% CI): 0.97 (0.61, 1.34) in males; ß (95% CI): 0.84 (0.63, 1.05) in females]. Each 1-unit increase in ln-transformed BHg, the SUA levels rose by 4.78 (95% CI: 0.01, 9.54) µmol/L for males and 3.81 (95% CI: 1.60, 6.03) µmol/L for females. The association between fish consumption with SUA levels was mediated by ln-transformed BHg with the percent mediated of 34.66% in males and 26.58% in females. It revealed that BHg played mediating roles in the elevation of SUA levels caused by fish consumption. This study's findings could promote the government to intervene in mercury pollution in fish, so as to ensure the safety of fish consumption.

Identification of lncRNA-mRNA network linking ferroptosis and immune infiltration to colon adenocarcinoma suppression.

Background: Colon adenocarcinoma (COAD) is one of the most common malignant tumors. The interplay involving ferroptosis between tumor and immune cells plays a crucial in cancer progression. However, the biological basis of this interplay in COAD development remains elusive. Methods: Transcriptome data of COAD samples were obtained from The Cancer Genome Atlas and National Center for Biotechnology Information databases. Using single-sample gene set enrichment analysis, we calculated the ferroptosis score (FS) and immune cell infiltration levels for each sample, leveraging the expression levels of genes related to ferroptosis and various immune cell types. Samples with FSs greater than the 75th percentile were classified into the high-FS subgroup, while those below the 25th percentile were categorized as the low-FS subgroup. Moreover, tumor tissue samples and adjacent normal tissue samples were collected from twenty colon patients. Using real-time quantitative polymerase chain reaction, we validated the expression of certain genes in these samples. Results: The COAD samples with high FSs experienced favorable survival probability and heightened sensitivity to anticancer drugs, with FSs negatively associated with the pathological stages. Moreover, the up-regulated genes in high-FS subgroup exhibited enrichment in immune-related pathways, suggesting a correlation between immunity and ferroptosis. Importantly, we discovered a key lncRNA-mRNA co-expression network linking tumor cell ferroptosis and immune infiltration (e.g., neutrophil) in the progression and classification of COAD. Further analysis identified several ferroptosis-related lncRNAs (e.g., RP11-399O19.9) within this network, indicating their potential roles in COAD progression and deserving in-depth study. Conclusions: Our findings provide novel insights into the underlying biological basis, particularly involving lncRNAs, at gene expression level associated with ferroptosis in COAD and cancer therapy. Nevertheless, further analysis and validation are required to expand the findings.

Dissecting diazirine photo-reaction mechanism for protein residue-specific cross-linking and distance mapping.

While photo-cross-linking (PXL) with alkyl diazirines can provide stringent distance restraints and offer insights into protein structures, unambiguous identification of cross-linked residues hinders data interpretation to the same level that has been achieved with chemical cross-linking (CXL). We address this challenge by developing an in-line system with systematic modulation of light intensity and irradiation time, which allows for a quantitative evaluation of diazirine photolysis and photo-reaction mechanism. Our results reveal a two-step pathway with mainly sequential generation of diazo and carbene intermediates. Diazo intermediate preferentially targets buried polar residues, many of which are inaccessible with known CXL probes for their limited reactivity. Moreover, we demonstrate that tuning light intensity and duration enhances selectivity towards polar residues by biasing diazo-mediated cross-linking reactions over carbene ones. This mechanistic dissection unlocks the full potential of PXL, paving the way for accurate distance mapping against protein structures and ultimately, unveiling protein dynamic behaviors.

Charge Redistribution in High-Entropy Perovskite Oxide Porous Nanotubes Boosts Nitrate Electroreduction to Ammonia.

High-entropy perovskite oxides are promising materials in the field of electrocatalysis due to their advantages such as large spatial composition regulation, entropy effects, and tunable material properties. However, the preparation of high-entropy perovskite oxides with stable and controllable structures still remains challenging. Herein, we fabricated a series of high-entropy perovskite oxide porous nanotubes (PNTs) by electrospinning as efficient electrocatalysts for the nitrate reduction reaction (NO3RR). We further revealed that the different diffusion and decomposition behaviors of metal ions and polymers during the calcination process are the key to the formation of high-entropy perovskite oxide PNTs. Especially, LaSrNiCoMnFeCuO3 PNTs show excellent performance of the NO3RR, achieving the maximum NH3 Faradaic efficiency of almost 100%, yield rate of 1657.5 µg h-1 mgcat.-1, and durable stability after successive cycling, being one of the best electrocatalysts for the NO3RR. The mechanism studies show that the charge redistribution induced by the multisite synergistic effect and abundant unsaturated sites in the high-entropy perovskite oxide PNTs favors the adsorption of NO3- and key intermediates and reduces the catalytic energy barrier, thus further achieving high NO3- conversion efficiency.

Nonclinical safety and immunogenicity assessment of a combined DTacP vaccine in animal models.

The (diphtheria, tetanus, and pertussis [acellular, component] [DTacP]) vaccine is a combined vaccine designed to prevent three potentially fatal diseases including pertussis, tetanus, and diphtheria in both children and adults. We utilized advanced technology to develop a novel DTacP vaccine that was previously unavailable in China. The nonclinical studies were performed to evaluate the immunogenicity, potential toxicity, and local tolerance of the vaccine in animal models. In the immunogenicity study, three batches of the vaccine were intraperitoneally administered to National Institutes of Health (NIH) mice, resulting in 100% seropositivity for all three batches. Additionally, antibody levels notably increased as the immunization dosage increased. In acute toxicity study, no mortality was observed among the animals during the 14-day observation period, and no abnormalities in clinical signs were reported. Active systemic anaphylaxis assessment in guinea pigs showed no evidence of serious allergic reactions in the vaccine groups. In the repeat-dose toxicity study, where five intramuscular doses were administered every 2 weeks, gross autopsy and histopathological examination revealed no vaccine-related systemic pathological changes in rats, with dose site irritant reactions mostly recovered at the end of recovery period. In conclusion, the vaccine demonstrated good local and systemic tolerance, supporting its clinical development.