Chemistry-Enabled Intercellular Enzymatic Labeling for Monitoring the Immune Effects of Cytotoxic T Lymphocytes In Vivo.

Monitoring the effector function of cytotoxic T lymphocytes (CTLs) in vivo remains a great challenge. Here, we develop a chemistry-enabled enzymatic labeling approach to evaluate the tumor-specific immune response of CTLs by precisely monitoring the interaction between CTLs and tumor cells. Staphylococcus aureus sortase A (SrtA) is linked to the CTL surface through bioconjugate chemistry and then catalyzes the transfer of fluorescent-labeled substrate, 5-Tamra-LPETG, to CTLs. Meanwhile, the tumor cells are specifically decorated with N-terminal glycine residues (G5 peptide) through the inherent glycolmetabolism of cathepsin B-specific cleavable triacetylated N-azidoacetyl-d-mannosamine (CB-Ac3ManNAz) and click chemistry. After the infiltration of engineered CTLs into the tumor tissues, the immune-synapse-mediated specific interaction of CTLs and tumor cells leads to the accurate fluorescent labeling of tumor cells through the SrtA-catalyzed 5-Tamra-LPETG transfer. Therefore, the immune effect of CTLs as well as the performance of immune drugs can be determined, providing a novel strategy for pushing ahead immunotherapy.

A fluorescence-enhanced method specific for furfural determination in Chinese Baijiu based on luminescent carbon dots and direct surface reaction.

Detecting the furfural concentration in Baijiu can be used to assess the quality of Baijiu, allowing for the optimization of processing techniques and the enhancement of overall quality. In this paper, a fluorescence-enhanced method based on carbon dots (o-CDs) is developed for the furfural determination in Chinese Baijiu. In an environment full-filled with ·SO4- and ·OH, furfural undergone a direct surface reaction with the ortho-diamino groups at o-CDs. The created furan-based imidazole increased the surface electron density, leading an emission enhancement and color changes from orange to green. Thereby, a linear fluorescence response of o-CDs-TA to furfural is established in water with a detection limit of 30.5 nM. Finally, after ethanol correction it is used to determine furfural in Chinese Baijiu with high precision and reproducibility, providing a new strategy with low-cost and high sensitivity. In particular, the idea of covalently connecting target molecule to the CDs surface via the assistance of free radical opens a new avenue to merge the nanoscale and molecular realms through implementing chemical role into carbon nanostructures.

An artificially evolved gene for herbicide-resistant rice breeding.

Discovering and engineering herbicide-resistant genes is a crucial challenge in crop breeding. This study focuses on the 4-hydroxyphenylpyruvate dioxygenase Inhibitor Sensitive 1-Like (HSL) protein, prevalent in higher plants and exhibiting weak catalytic activity against many ß-triketone herbicides (ß-THs). The crystal structures of maize HSL1A complexed with ß-THs were elucidated, identifying four essential herbicide-binding residues and explaining the weak activity of HSL1A against the herbicides. Utilizing an artificial evolution approach, we developed a series of rice HSL1 mutants targeting the four residues. Then, these mutants were systematically evaluated, identifying the M10 variant as the most effective in modifying ß-THs. The initial active conformation of substrate binding in HSL1 was also revealed from these mutants. Furthermore, overexpression of M10 in rice significantly enhanced resistance to ß-THs, resulting in a notable 32-fold increase in resistance to methyl-benquitrione. In conclusion, the artificially evolved M10 gene shows great potential for the development of herbicide-resistant crops.

Identification and genomic analyses of a Streptococcus suis ST25 strain associated with the first human septicemia in mainland China.

Streptococcus suis (S. suis) is a Gram-positive bacterium and the main culprit behind zoonotic outbreaks, posing a serious threat to public health. The prevalent strains in China are mainly of sequence types (ST) 1 and 7, with few cases of human infections caused by other sequence type being reported. This study presents the first isolation of a ST25 strain from the blood of a septicemic patient. A 57-year-old febrile patient was admitted to a hospital in Hainan of China, diagnosed as septicemia and hepatic dysfunction. A strain of S. suis was isolated from blood culture and confirmed to be serotype 2 and ST25 through 16S rRNA sequencing and whole-genome sequencing, and its genome was further analyzed for gene functions and presence of drug resistance genes. The full-length genome of strain HN28 spans 2,280,124 bp and encodes a total of 2291 proteins. Genes annotated in COG, GO, KEGG, CAZy, and PHl databases accounted for 75.38 %, 69.14 %, 55.35 %, 4.58 %, and 11.87 % of the total predicted proteins, respectively. Virulence factor analysis revealed the presence of seven putative virulence genes in strain HN28. Analysis using the CARD database identified 51 resistance genes in HN28, alongside abundant exocytosis systems. These findings underscore the occurrence of S. suis infections in humans caused by less common ST, emphasizing the need for enhanced epidemiological investigations and monitoring of S. suis infections in the human population.

Pannonibacter tanglangensis sp. nov., a New Species Isolated from Pond Sediment.

Two bacterial strains (XCT-34T and XCT-53) isolated from sediment samples of an artificial freshwater reservoir were analyzed using a polyphasic approach. The two isolates are aerobic, Gram-stain-negative, oxidase-negative, catalase-positive, motile with polar flagella, rod-shaped, and approximately 1.4-3.4 × 0.4-0.9 µm in size. Phylogenetic analyses based on 16S rRNA gene and whole-genome sequences showed that the two strains formed a distinct branch within the evolutionary radiation of the genus Pannonibacter, closest to Pannonibacter carbonis Q4.6T (KCTC 52466). Furthermore, lower than threshold average nucleotide identity values (ANI, 85.7-86.4%) and digital DNA-DNA hybridization values (dDDH, 22.3-30.5%) of the two strains compared to the nearest type strains also confirmed that they represented a novel species. Genomic analyses, including annotation of the KEGG pathways, prediction of the secondary metabolism biosynthetic gene clusters and PHI phenotypes, supported functional inference and differentiation of the strains from the closely related taxa. Results of chemotaxonomic and physiological studies revealed that their distinct phenotypic characteristics distinguished them from existing Pannonibacter species. Thus, the two strains are considered to represent a novel species of Pannonibacter, for which the name of Pannonibacter tanglangensis sp. nov. is proposed, with XCT-34T (= KCTC 82332T = GDMCC 1.1947T) as the respective type strain.

Magilock: a reliable control triggering method in multi-channel eye-control systems.

Eye-tracking technology brings a different human-computer interaction experience to users because of its intuitive, natural, and hands-free operation characteristics. Avoiding the Midas touch problem and improving the accuracy of interaction are among the main goals of the research and development of eye-control systems. This study reviews the methods and limitations of research on avoiding the Midas touch problem. For typical control clicking operations with low fault tolerance, such as mode switching and state selection in an eye-control system, this study proposes Magilock, a more reliable control triggering method with a high success rate in multi-channel eye-control systems. Magilock adds a control pre-locked mechanism between the two interactive steps of eye-control channel positioning control and other interactive channel triggering controls in the multi-channel eye-control system. This effectively avoids incorrect control triggering caused by multi-channel coordination disorder and gaze-point drift. This study also conducted ergonomic experiments to explore the lock and unlock times of the control pre-locked mechanism in Magilock. Taking into account the experimental data and subjective evaluation of the participants, we recommend setting the lock time and the unlock time of Magilock to 200 ms.

Expression, purification, and characterization of transmembrane protein homogentisate solanesyltransferase.

Homogentisate solanesyltransferase (HST) is a crucial enzyme in the plastoquinone biosynthetic pathway and has recently emerged as a promising target for herbicides. In this study, we successfully expressed and purified a stable and highly pure form of seven times transmembrane protein Chlamydomonas reinhardtii HST (CrHST). The final yield of CrHST protein obtained was 12.2 mg per liter of M9 medium. We evaluated the inhibitory effect on CrHST using Des-Morpholinocarbony Cyclopyrimorate (DMC) and found its IC50 value to be 3.63 ± 0.53 µM, indicating significant inhibitory potential. Additionally, we investigated the substrate affinity of CrHST with two substrates, determining the Km values as 22.76 ± 1.70 µM for FPP and 48.54 ± 3.89 µM for HGA. Through sequence alignment analyses and three-dimensional structure predictions, we identified conserved amino acid residues forming the active cavity in the enzyme. The results from molecular docking and binding energy calculations indicate that DMC has a greater binding affinity with HST compared to HGA. These findings represent substantial progress in understanding CrHST's properties and potential for herbicide development. KEY POINTS: • First high-yield transmembrane CrHST protein via E. coli system • Preliminarily identified active cavity composition via activity testing • Determined substrate and inhibitor modes via molecular docking.

Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates.

BACKGROUND: Resistance to clarithromycin (CLA) and levofloxacin (LFX) of Helicobacter pylori (H. pylori) is increasing in severity, and successful eradication is essential. Presently, the eradication success rate has greatly declined, leaving a large number of patients with previous treatment histories. AIM: To investigate secondary resistance rates, explore risk factors for antibiotic resistance, and assess the efficacy of susceptibility-guided therapy. METHODS: We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023. Participants underwent a string test after an overnight fast. The gastric juice was obtained and transferred to vials containing storage solution. Subsequently, DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction (qPCR). Demographic information was also analyzed as part of the study. Based on these results, the participants were administered susceptibility-guided treatment. Efficacy was compared with that of the empiric treatment group. RESULTS: A total of 132 individuals tested positive for the H. pylori ureA gene by qPCR technique. CLA resistance rate reached a high level of 82.6% (n = 109), LFX resistance rate was 69.7% (n = 92) and dual resistance was 62.1% (n = 82). Gastric symptoms [odds ratio (OR) = 2.782; 95% confidence interval (95%CI): 1.076-7.194; P = 0.035] and rural residence (OR = 5.152; 95%CI: 1.407-18.861; P = 0.013) were independent risk factors for secondary resistance to CLA and LFX, respectively. A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment, respectively. The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5% (77/102) and 59.0% (59/411) by the intention-to-treat (ITT) analysis and 90.6% (77/85) and 70.2% (59/84) by the per-protocol (PP) analysis, respectively. The eradication rates of these two treatment strategies were significantly different in both ITT (P = 0.001) and PP (P = 0.012) analyses. CONCLUSION: H. pylori presented high secondary resistance rates to CLA and LFX. For patients with previous treatment failures, treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Bacteroid cerium oxide particles promote macrophage polarization to achieve early vascularization and subsequent osseointegration around implants.

The establishment of an osseointegration is crucial for the long-term stability and functionality of implant materials, and early angiogenesis is the key to successful osseointegration. However, the bioinertness of titanium implants affects osseointegration, limiting their clinical application. In this study, inspired by the rapid polarization of macrophages following the phagocytosis of bacteria, we developed bacteroid cerium oxide particles; these particles were composed of CeO2 and had a size similar to that of Bacillus (0.5 µ m). These particles were constructed on the implant surfaces using a hydrothermal method. In vitro experiments demonstrated that the particles effectively decreased the reactive oxygen species (ROS) levels in macrophages (RAW264.7). Furthermore, these particles exerted effects on M1 macrophage polarization, enhanced nitric oxide (NO) secretion to promote vascular regeneration, and facilitated rapid macrophage transition to the M2 phenotype. Subsequently, the particles facilitated human umbilical vein endothelial cell (HUVEC) migration. In vivo studies showed that these particles rapidly stimulated innate immune responses in animal models, leading to enhanced angiogenesis around the implant and improved osseointegration. In summary, the presence of bacteroid cerium oxide particles on the implant surface regulated and accelerated macrophage polarization, thereby enhancing angiogenesis during the immune response and improving peri-implant osseointegration.

The Construction of Three-Layered Biomimetic Arterial Graft Balances Biomechanics and Biocompatibility for Dynamic Biological Reconstruction.

The process of reconstructing an arterial graft is a complex and dynamic process that is subject to the influence of various mechanical factors, including tissue regeneration and blood pressure. The attainment of favorable remodeling outcomes is contingent upon the biocompatibility and biomechanical properties of the arterial graft. A promising strategy involves the emulation of the three-layer structure of the native artery, wherein the inner layer is composed of polycaprolactone (PCL) fibers aligned with blood flow, exhibiting excellent biocompatibility that fosters endothelial cell growth and effectively prevents platelet adhesion. The middle layer, consisting of PCL and polyurethane (PU), offers mechanical support and stability by forming a contractile smooth muscle ring and antiexpansion PU network. The outer layer, composed of PCL fibers with an irregular arrangement, promotes the growth of nerves and pericytes for long-term vascular function. Prioritizing the reconstruction of the inner and outer layers establishes a stable environment for intermediate smooth muscle growth. Our three-layer arterial graft is designed to provide the blood vessel with mechanical support and stability through nondegradable PU, while the incorporation of degradable PCL generates potential spaces for tissue ingrowth, thereby transforming our graft into a living implant.

Mechanism of enhanced microalgal biomass and lipid accumulation through symbiosis between a highly succinic acid-producing strain of Escherichia coli SUC and Aurantiochytrium sp. SW1.

Microalgae, known for rapid growth and lipid richness, hold potential in biofuels and high-value biomolecules. The symbiotic link with bacteria is crucial in large-scale open cultures. This study explores algal-bacterial interactions using a symbiotic model, evaluating acid-resistant Lactic acid bacteria (LAB), stress-resilient Bacillus subtilis and Bacillus licheniformis, and various Escherichia coli strains in the Aurantiochytrium sp. SW1 system. It was observed that E. coli SUC significantly enhanced the growth and lipid production of Aurantiochytrium sp. SW1 by increasing enzyme activity (NAD-IDH, NAD-ME, G6PDH) while maintaining sustained succinic acid release. Optimal co-culture conditions included temperature 28 °C, a 1:10 algae-to-bacteria ratio, and pH 8. Under these conditions, Aurantiochytrium sp. SW1 biomass increased 3.17-fold to 27.83 g/L, and total lipid content increased 2.63-fold to 4.87 g/L. These findings have implications for more efficient microalgal lipid production and large-scale cultivation.

Effect of pre-pregnancy obesity on trimester-specific thyroid dysfunction / 上海预防医学

ObjectiveTo explore the risk of different levels of pre-pregnancy obesity on trimester-specific thyroid dysfunction. MethodsQuestionnaire information， blood samples， and urine samples from a 2017 pregnancy cohort study in Shanghai， China were collected. A total of 2 455 pregnant women were included in the analysis. Pre-pregnancy BMI was calculated based on the height and self-reported pre-pregnancy weight. Serum TSH， total thyroxine （TT4）， free thyroxine （FT4）， total triiodothyronine （TT3）， free triiodothyronine （FT3）， thyroid globulin antibody（TgAb）， and Thyroid peroxidase antibody （TPOAb） were measured using the electrochemiluminescence method. Urine iodine levels were measured using the acid digestion method. Levels of thyroid function indexes of pregnant women with different degrees of obesity during pre-pregnancy were compared， and trimester-specific thyroid dysfunction was evaluated according to the reference range of trimester-specific thyroid hormone established by this cohort. Multivariate logistic regressions analysis was used to assess the correlation between pre-pregnancy obesity and trimester-specific thyroid dysfunction. ResultsAs the degree of obesity increased， maternal levels of FT3 and TT3 gradually increased during pregnancy （P<0.001， P=0.001）， while FT4 levels gradually decreased （P=0.001）. Multivariate logistic regression analysis showed that compared with the normal weight group， pregnant women who were overweight or obesity before pregnancy had a significantly higher risk of hypothyroxinemia （OR=3.85， 95%CI： 2.08‒7.14， P<0.001） and high TT3 （OR=2.78， 95%CI： 1.45‒5.26， P=0.002） during pregnancy. ConclusionPre-pregnancy overweight or obesity can increase the risk of thyroid dysfunction during pregnancy.

A case-control study on gut microbiota diversity and species composition in obese/overweight children aged 2-6 years in Shanghai / 环境与职业医学

Background Multiple studies have shown a close relationship between changes in gut microbiota composition and obesity, and research results are influenced by factors such as race and geographical location, but there are few studies on children. Objective To analyze the diversity of gut microbiota related to obesity in a population of 2-6 years old, observe the distribution characteristics and species differences of gut microbiota between obese/overweight and normal weight groups, and explore the association betweenobese/overweight and gut microbiota diversity. Methods Fecal samples were collected from 74 children aged 2-6 years in Shanghai, including 18 obese/overweight individuals, 6 males and 12 females (male to female ratio of 1∶2), and 56 normal weight individuals, 18 males and 38 females (male to female ratio is nearly 1∶2). The 16S rDNA was extracted from bacteria in fecal samples, followed by PCR amplification, cDNA construction, and high-throughput sequencing. Naive Bayes algorithm was used to perform taxonomic analysis (phylum, class, order, family, genus, species) and community diversity analysis (Sobs index, Shannon index, Shannoneven index, Coverage index, PD index, and principal co-ordinates analysis) on representative sequences and abundance of amplicon sequence variants (ASV). Wilcoxon rank sum test, P-value multiple test correction, and analysis of similarities were used to test differences between the two groups to obtain information on the distribution characteristics and species differences of intestinal microbiota in children. Results Seventy-four fecal samples were sequenced, and the sequencing results were subjected to quality control and filtering. A total of 4905306 optimized sequences were obtained, resulting in 1860 ASVs. The diversity data analysis of ASVs generated 889 species annotation results at 8 taxonomic levels. The alpha diversity analysis showed that the richness (Sobs index), diversity (Shannon index), evenness (Shannoneven index), and phylogenetic diversity (PD index) of fecal community of the obese/overweight children were increased compared to those of the normal weight children, but there were no statistical differences between the two groups (P>0.05). The beta diversity analysis showed that there was little difference in the composition of microbial species between the two groups, and no significant clustering separation was observed. The results of species composition analysis at phylum, order, family, and genus levels of 74 samples showed a consistent core microbiota structure in the two groups of gut microbiota, but there were differences in microbiota composition. The differences in microbial community composition between the two groups were manifested at the taxonomic levels of order, family, and genus, among which phylum Firmicutes, order Erysipelotrichales, family Erysipelatocyclostridiaceae, genus Erysipelotrichaceae_ UCG-003 and genus Catenibacterium were significantly enriched in the obese/overweight group and contributed significantly to the phenotypic difference of obese/overweight [linear discriminant analysis (LDA)=3.72, P<0.01; LDA=3.29, P<0.05). Phylum Proteobacteria, order Enterobacterales, family Enterobacteriaceae, genus unclassified was significantly enriched in the normal weight group and contributed significantly to the phenotypic difference of normal body weight (LDA=3.93, P<0.05). Conclusion The richness and diversity of gut microbiota in obese/overweight children aged 2-6 years in Shanghai are increased, but there is no difference compared to normal weight children. There is a difference in the composition of gut microbiota between the obese/overweight group and the normal weight group.

The regulatory mechanism and research status of deiodinating isozymes at the cellular level of thyroid hormone levels / 中华内分泌外科杂志

As color doppler ultrasound listed as the thyroid to regular physical examination project, the positive detection rate of benign and malignant thyroid diseases has increased year by year. The population of patients after thyroid surgery is getting larger and larger, however, the research on how to replace the absent thyroid with exogenous thyroid hormone is not perfect. As the switch of thyroid hormone activation and deactivation, deiodinase plays an important role in maintaining the internal environment of human body. The expression of these enzymes will change with the different needs of each organ in the individual. In the past, many authors have made a detailed description of deiodinase in basic medicine, but the principle of action in clinical aspects is relatively lacking. In this paper, the mechanism of deiodinase was reviewed through literature reading, to explore the basic principle of deiodinase in exogenous thyroid hormone supplementation after thyroid surgery.

AI Rudi's Experience in Treating Acne with Triple Chinese Medicinal Groups Combined with Chinese Medicinal Mask / 中医杂志

To summarize the clinical experience of Professor AI Rudi in treating acne with triple Chinese medicinal groups combined with Chinese medicinal mask. It is believed that the pathogenesis and treatment of male and female acne are different. The key mechanism of male acne is the dysfunction of the "lung-spleen and stomach-large intestine" axis， and the method of three jiao differentiation should be used. Clinically， the triple Chinese medicinal group， Rendongteng （Lonicera japonica） - Qishe （Portulaca oleracea） - Shicangpu （Acorus gramineus）， can scatter wind to relieve heat， and diffuse and disperse upper jiao； group Baihua Sheshecao （Scleromitrion diffusum） - Baixianpi （Dictamnus dasycarpus） - Tanxiang （Santalum album） can clear heat and drain dampness， and regulate middle jiao； group Huaimi （Styphnolobium japonicum） - Juemingzi （Senna tora） - Baizhu （Atractylodes macrocephala） can tonify and moisten to unblock the lower jiao. The core mechanism of female acne is the imbalance of the function of the "liver and kidney- Tiangui （reproduction-stimulating essence， corresponds with the tenth heavenly stem） - Chong and ren" axis， and the method of staged tratment based on menstrual cycle should be used. Before the menstrual period， group Tusizi （Cuscuta chinensis） - Yujing （Curcuma longa） - Qianghuoyu （Hansenia forbesii） can tonify kidney and relax liver； during the menstrual period， group Chuanxiong （Rhizoma Ligustici Chuangxiong） - Yimucao （Leonurus japonicus）- Cansha （Bombycis Faeces） can invigorate blood and regulate menstrual flow； after the menstrual period， group Huangjing （Polygonatum sibiricum） - Shanyurou （Corni Fructus） - Roucongrong （Cistanche deserticola） can nourish blood， assist yang and boost yin. Meanwhile， we attached importance to the internal and external treatment. Based on the internal administration of traditional Chinese medicine， Chinese medicinal masks were used for external application， commonly used in self-prescribed Xianglian Jinhuang Powder （香连金黄散） combined with Huoxue Powder （活血散） as the prescription for Chinese medicinal mask.

Establishment and Validation of a Model for Differential Diagnosis between Aortic Dissection and Myocardial Infarction / 医学研究杂志

Objective Most of the clinical manifestations of aortic dissection and myocardial infarction are chest pain,which can easily lead to misdiagnosis and disastrous consequences.Therefore,this study intends to establish a differential diagnosis model and verify it in order to achieve early accurate prediction.Methods The relevant information of 200 patients with myocardial infarction and 120 pa-tients with aortic dissection diagnosed in the Second Affiliated Hospital of Zhengzhou University was collected,including age,gender,blood routine examination,electrolytes,markers of myocardial necrosis and blood coagulation function at admission.The patients were di-vided into myocardial infarction group and aortic dissection group.The independent risk factors were found out through t-test,AN OVA and binary Logistic regression analysis,and the nomogram was further drawn using R language to develop and validate the differential diag-nosis scoring table.Results The procalcitonin,prothrombin time(PT)、international normalized ratio(INR)、fibrin degradation product(FDP),D-dimer,white blood cell(WBC),percentage of neutrophil,percentage of lymphocyte,absolute value of neutrophil,absolute value of lymphocyte,C-reactive protein,cardiac troponin T(cTNT)、creatine kinase isozyme(CK-MB),systolic blood pressure of pa-tients in the two groups were statistically significant(P＜0.05),There was no significant difference in other indexes(P＞0.05).Binary Logistic regression analysis further showed that procalcitonin,D-dimer,C-reactive protein and systolic blood pressure were independent risk factors for diagnosing aortic dissection,while percentage of lymphocyte and absolute value of lymphocyte were independent risk factors for diagnosing myocardial infarction.According to the validation results of the score table developed by the nomogram,the the area under the receiver operating characteristic curve was 0.978,and the best cut-off value was 40.70 points.The sensitivity and specificity were 92.5％and 96.0％.Conclusion This study confirms that procalcitonin,D-dimer,C-reactive protein and systolic blood pressure are independent risk factors for diagnosing aortic dissection,while percentage of lymphocyte and absolute value of lymphocyte are independent risk factors for diagnosing myocardial infarction.The differential diagnosis scoring table proposed in this study can effectively differentiate patients with aortic dissection and myocardial infarction at an early stage,so as to guide further clinical diagnosis and treatment.

Analysis of Pharmacokinetics/Pharmacodynamics Compliance and Influencing Factors of Meropenem Concentration in Patients with Augmented Renal Clearance / 医药导报

Objective To explore the pharmacokinetics/pharmacodynamics(PK/PD)parameters and influencing factors in patients with augmented renal clearance(ARC)to provide the basis for the rational use of meropenem.Methods Using the method of retrospective study,the patients with increased renal clearance who used meropenem monitored the concentration from January 2018 to December 2021.The PK/PD parameters of meropenem were analyzed,and multiple linear retrospective analyses discussed the influencing factors of meropenem valley concentration.Results A total of 58 patients were included in the study,and the trough concentration was 1.35[0.23,1.86]μg·mL-1,taking 100%fT＞MIC as PK/PD target value,the compliance rate was 20.69%.The compliance rate of daily dose＜3 g·d-1 was 8.70%,and≥3 g·d-1 was 31.43%,the difference was statistically significant.With MIC of 0.5,1,2,4,and 8 μg·mL-1,PK/PD compliance rates were 62.07%,48.28%,20.69%,8.62%and 0.Respectively.Multiple linear retrospective analyses showed that dose was an independent factor affecting meropenem valley concentration.Conclusion The PK/PD compliance rate of meropenem in patients with augmented renal clearance is low,even if MIC≤0.5 μg·mL-1,the routine dose is difficult to achieve the ideal PK/PD,so the clinical should recognize ARC and perform TDM as soon as possible,and use TDM to guide the medication regimen of meropenem for ARC patients.

Effect of ultrasound-guided internal branch of superior laryngeal nerve block on quality of anesthesia recovery in patients undergoing intracranial tumor surgery: a retrospective study / 中华麻醉学杂志

Objective:To evaluate the effect of ultrasound-guided internal branch of superior laryngeal nerve(ibSLN) block on the quality of anesthesia recovery in the patients undergoing intracranial tumor surgery.Methods:The data from patients of either gender, aged 18-65 yr, with a body mass index of 18-28 kg/m 2, who underwent intracranial tumor surgery from December 2022 to October 2023, were retrospectively collected. Patients were divided into control group (group C) and ultrasound-guided ibSLN block group (group U). Bilateral ibSLN block was performed with 0.375% ropivacaine hydrochloride 2 ml.The tracheal extubation time, emergence time, development of cardiovascular events within 15 min after extubation, emergence agitation, Ramsay sedation score, Steward recovery score, visual analogue scale scores at 10 min after extubation and development of postoperative sore throat and hoarseness in postanesthesia care unit were recorded. Results:Compared with group C, the incidence of emergence agitation, Ramsay sedation score, visual analogue scale scores and sore throat were significantly decreased, the incidence of hoarseness was increased ( P<0.05), and no significant change was found in the extubation time, emergence time and Steward recovery score in group U( P>0.05). No hypertension, hypotension, tachachycardia and bradycardia were found in two groups. Conclusions:Ultrasound-guided ibSLN block can improve the quality of anesthesia recovery in the patients undergoing intracranial tumor surgery.

Discovery and Development of 4-Hydroxyphenylpyruvate Dioxygenase as a Novel Crop Fungicide Target.

Plant pathogenic fungi pose a significant threat to crop yields and quality, and the emergence of fungicide resistance has further exacerbated the problem in agriculture. Therefore, there is an urgent need for efficient and environmentally friendly fungicides. In this study, we investigated the antifungal activity of (+)-Usnic acid and its inhibitory effect on crop pathogenic fungal 4-hydroxyphenylpyruvate dioxygenases (HPPDs) and determined the structure of Zymoseptoria tritici HPPD (ZtHPPD)-(+)-Usnic acid complex. Thus, the antifungal target of (+)-Usnic acid and its inhibitory basis toward HPPD were uncovered. Additionally, we discovered a potential lead fungicide possessing a novel scaffold that displayed remarkable antifungal activities. Furthermore, our molecular docking analysis revealed the unique binding mode of this compound with ZtHPPD, explaining its high inhibitory effect. We concluded that HPPD represents a promising target for the control of phytopathogenic fungi, and the new compound serves as a novel starting point for the development of fungicides and dual-purpose pesticides.

α-Synuclein induces deficiency in clathrin-mediated endocytosis through inhibiting synaptojanin1 expression.

Parkinson's disease (PD) is an age-related chronic neurological disorder, mainly characterized by the pathological feature of α-synuclein (α-syn) aggregation, with the exact disease pathogenesis unclear. During the onset and progression of PD, synaptic dysfunction, including dysregulation of axonal transport, impaired exocytosis, and endocytosis are identified as crucial events of PD pathogenesis. It has been reported that over-expression of α-syn impairs clathrin-mediated endocytosis (CME) in the synapses. However, the underlying mechanisms still needs to be explored. In this study, we investigated the molecular events underlying the synaptic dysfunction caused by over-expression of wild-type human α-syn and its mutant form, involving series of proteins participating in CME. We found that excessive human α-syn causes impaired fission and uncoating of clathrin-coated vesicles during synaptic vesicle recycling, leading to reduced clustering of synaptic vesicles near the active zone and increased size of plasma membrane and number of endocytic intermediates. Furthermore, over-expressed human α-syn induced changes of CME-associated proteins, among which synaptojanin1 (SYNJ1) showed significant reduction in various brain regions. Over-expression of SYNJ1 in primary hippocampal neurons from α-syn transgenic mice recovered the synaptic vesicle density, clustering and endocytosis. Using fluorescence-conjugated transferrin, we demonstrated that SYNJ1 re-boosted the CME activity by restoring the phosphatidylinositol-4,5-bisphosphate homeostasis. Our data suggested that over-expression of α-syn disrupts synaptic function through interfering with vesicle recycling, which could be alleviated by re-availing of SYNJ1. Our study unrevealed a molecular mechanism of the synaptic dysfunction in PD pathogenesis and provided a potential therapeutic target for treating PD.