L-phosphinothricin (L-PPT) is an efficient broad-spectrum herbicide. To realize the multi-enzyme catalytic preparation of L-PPT, we constructed an engineered strain Escherichia coli YM-1 for efficient expression of D-amino acid transaminase, which could catalyze the generation of the intermediate 2-oxo-4-[(hydroxymethylphosphonyl)] butyric acid (PPO) from D-phosphinothricin (D-PPT). In addition, E. coli pLS was constructed to co-express glutamate dehydrogenase and glucose dehydrogenase, which not only catalyzed the generation of L-PPT from PPO but also regenerated the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH). A fed-batch fermentation process was then established for E. coli YM-1 and pLS, and the apparent activities of D-amino acid transaminase and glutamate dehydrogenase were increased by 22.68% and 100.82%, respectively, compared with those in shake flasks. The process parameters were optimized for the catalytic preparation of L-PPT by whole-cell cascade of E. coli YM-1 and pLS with D, L-PPT as the substrate. After reaction for 8 h, 91.36% conversion of D-PPT was achieved, and the enantiomeric excess of L-PPT reached 90.22%. The findings underpin the industrial production of L-PPT.
Escherichia coli/enzymology* ; Aminobutyrates/metabolism* ; Glutamate Dehydrogenase/biosynthesis* ; Glucose 1-Dehydrogenase/biosynthesis* ; Herbicides/metabolism* ; Multienzyme Complexes/metabolism* ; Transaminases/metabolism* ; Phosphinic Acids/metabolism*

Objective To perform laboratory detection and molecular traceability analysis on a case of imported kala-azar in Shenzhen to determine the infection strain. Methods Bone marrow puncture fluid and blood samples from a case of kala-azar in Shenzhen were collected for laboratory tests. The patient's bone marrow puncture fluid smears were stained with Giemsa and examined under a microscope. Blood samples were examined for antibodies using the rk39 visceral leishmania rapid diagnostic reagent. Whole blood DNA was extracted, and the ITS-1 sequence was amplified by PCR, sequenced and aligned, and a phylogenetic tree was constructed based on the ITS-1 sequence. Results Microscopic examination of the patient's bone marrow smears revealed a large number of Leishmania amastigotes without flagella, confirming the diagnosis of kala-azar. The patient's blood was tested positive with the rk39 rapid diagnostic reagent, and PCR amplification yielded an ITS-1 gene product sequence that matched the expected size. Sequence alignment with the NCBI database showed 100% sequence similarity with the ITS-1 gene sequence of Leishmania infantum, confirming the infecting strain as Leishmania infantum. Phylogenetic tree construction of the amplified ITS-1 sequence revealed clustering into a clade with Leishmania infantum , and close to KC347299, one of the reference sequence selected. Conclusions The case of kala-azar in Shenzhen was caused by Leishmania infantum. Kala-azar still occurs in China, so the diagnostic technology of medical personnel in non-epidemic areas should be strengthened so that they can actively use new diagnostic technologies to assist in diagnosis, thus improving their prevention and control ability of Leishmania parasites.

Objective:To investigate the sense of coherence, job stressors and mental health status of nurses practitioners, and analyze the correlation among them.Methods:In September 2020, nurses practitioners in Chengdu City, Sichuan Province were selected as the research objects by convenience sampling method. The Sense of Coherence Scale, Nurses' Job Stressors Scale and SCL-90 were used to investigate their sense of coherence, job stressors and mental health status, respectively. Pearson correlation test was used to analyze the correlation among them, and the structural equation model was constructed to explore the mechanism of them.Results:A total of 1693 nurse practitioners were included. The total scores of sense of coherence, job stressors and SCL-90 were (65.00±14.01) points, (69.08±18.38) points and (129.68±52.99) points, respectively. The mean scores of all dimensions of sense of coherence of nurse practitioners were negatively correlated with the mean scores of all dimensions of job stressors and SCL-90 ( P<0.001). And there were positive correlations between the mean scores of all dimensions of job stressors and the mean scores of all dimensions of SCL-90 ( P<0.001). The structural equation model fitted well. The path coefficient between job stressors and sense of coherence was -0.372 ( P<0.001), and the path coefficient between sense of coherence and SCL-90 score was -0.647 ( P<0.001) . Conclusion:The sense of coherence plays a significant buffering role in job stressors and mental health of nurses practitioners. Nursing managers should be committed to improving the level of sense of coherence of nurses, enhance the happiness of nurses at work, and improve their mental health level.

Alzheimer's disease(AD) is a common neurodegenerative disease with increasing incidence rate. Up to now,there is no ideal treatment for AD. It has become a public health problem worldwide. Traditional Chinese medicine (TCM) believes that kidney deficiency is the key symptomatic element of deterioration and temporal progression symptoms,accompanied by the AD process. The treatment of tonifying kidneys,supplementing essence and replenishing marrow is the fundamental method for AD in TCM. Clinical studies have shown that kidney-tonifying formula can significantly improve the cognitive function and daily ability of patients with mild and moderate AD and have no obvious adverse reactions. Its mechanism of action may be related to the protection of nerves,reduction of β-amyloid (Aβ) level in the brain,inhibition of inflammatory factors activation and anti-oxidative stress. Besides reviewing the clinical and pharmacological research progress of kidney-tonifying formula for AD,this article also discusses the advantages and shortcomings of kidney-tonifying formula in the prevention and treatment of AD based on TCM theory and modern medical research. The aim of this study is to provide references of kidney nourishing therapy in TCM for the prevention and treatment of neurodegenerative diseases.

Objective:To summarize the best evidence of exercise management of tumor-associated sarcopenia and provide reference for medical personnel to formulate individualized exercise intervention plans.Methods:BMJ Best Practice, UpToDate, Cochrane Library, Embase, PubMed, CINAHL, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang database, National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, and other databases were searched by computer for literature on exercise intervention for patients with tumor-associated sarcopenia, including clinical decision making, guidelines, expert consensus, evidence summary and systematic reviews. The search period was from the establishment of the databases to April 23, 2023. Two researchers independently conducted literature quality evaluation, evidence extraction, and integration.Results:A total of 12 articles were included, including 4 guidelines, 3 expert consensus papers, and 5 systematic reviews. A total of 32 pieces of evidence were summarized from five aspects, including exercise evaluation, exercise timing, exercise plan, exercise management, and evaluation indicators.Conclusions:This study summarizes the best evidence for exercise intervention in patients with tumor-associated sarcopenia and suggestes that medical staff should apply the proof according to the clinical context and the patient's wishes.

Objective:To investigate the sense of coherence, job stressors and mental health status of nurses practitioners, and analyze the correlation among them.Methods:In September 2020, nurses practitioners in Chengdu City, Sichuan Province were selected as the research objects by convenience sampling method. The Sense of Coherence Scale, Nurses' Job Stressors Scale and SCL-90 were used to investigate their sense of coherence, job stressors and mental health status, respectively. Pearson correlation test was used to analyze the correlation among them, and the structural equation model was constructed to explore the mechanism of them.Results:A total of 1693 nurse practitioners were included. The total scores of sense of coherence, job stressors and SCL-90 were (65.00±14.01) points, (69.08±18.38) points and (129.68±52.99) points, respectively. The mean scores of all dimensions of sense of coherence of nurse practitioners were negatively correlated with the mean scores of all dimensions of job stressors and SCL-90 ( P<0.001). And there were positive correlations between the mean scores of all dimensions of job stressors and the mean scores of all dimensions of SCL-90 ( P<0.001). The structural equation model fitted well. The path coefficient between job stressors and sense of coherence was -0.372 ( P<0.001), and the path coefficient between sense of coherence and SCL-90 score was -0.647 ( P<0.001) . Conclusion:The sense of coherence plays a significant buffering role in job stressors and mental health of nurses practitioners. Nursing managers should be committed to improving the level of sense of coherence of nurses, enhance the happiness of nurses at work, and improve their mental health level.

Abstract: Objective　To analyze and understand the mutations of drug resistance genes in imported Plasmodium falciparum in Shenzhen, aiming to assess the efficacy of antimalarial drugs and guide effective drug use. Methods A total of 85 samples from individuals with imported Plasmodium falciparum confirmed by fluorescence quantitative polymerase chain reaction (PCR) in Shenzhen from 2022 to 2023 were collected and genomic DNA was extracted. Nested PCR was used to amplify resistance genes, including Plasmodium falciparum Kelch 13 (PfK13), multidrug resistance gene 1 (Pfmdr1), chloroquine resistance transporter (Pfcrt), dihydrofolate reductase (Pfdhfr), and dihydropteroate synthase (Pfdhps) genes. Bidirectional sequencing was conducted, and mutations in these resistance genes were analyzed using MEGA11.06 software. Results　The study found one missense mutation (S549P) and four synonymous mutations in PfK13. For Pfmdr1, 62.69% of the samples showed Y184F mutation, and no N86Y mutation was detected. No mutations at positions 72 and 73 were detected in the Pfcrt gene, while mutations at M74I, N75E, and K76T accounted for 17.46%, 15.87%, and 15.87%, respectively. The wild-type of Pfcrt gene is dominant (82.54%, 52), followed by the triple mutant I74E75T76 (15.87%, 10). The most common mutation type for Pfdhfr is I51R59N108 (91.78%, 67), followed by the wild type (2.74%, 2). More than half (60.32%, 38) of the Pfdhps samples were wild-type, with single mutation K540E being the most common mutation type. S436A, G437A, K540E, A581G, A613S, I431V, G556K, and G579E site mutations were detected. Among the Pfdhfr-Pfdhps combination mutations, I51R59N108-E540 was the most frequent combination mutation (11.48%), with 59.02% of samples showing solitary Pfdhfr mutations. Conclusions In this study, PfK13 mutation rates were low, with no reported resistance mutations. The Y184F mutation emerged as the dominant Pfmdr1 mutation, with no detection of N86Y. For Pfcrt, the wild-type was dominant, followed by the I74E75T76 triple mutation variant. Triple mutant I51R59N108 of Pfdhfr was very common, and our study did not find Pfdhfr Pfdhps completely resistant and super resistant mutants, but there were other quintuple and septuple mutant types. In the future, it is crucial to continue to strengthen the monitoring of malaria parasite resistance genes and to further integrate in vivo efficacy monitoring to effectively guide clinical drug use.

Background The thyroid gland is one of the organs sensitive to ionizing radiation, and there are few studies on the effects of long-term exposure to low doses of ionizing radiation on the thyroid gland of radiation workers. Objective To investigate thyroid abnormalities in workers in medical radiology departments in Guangdong Province and to identify potential influencing factors of thyroid abnormalities. Methods A total of 1657 radiation workers from 48 hospitals in Guangdong Province were selected as survey subjects using convenience sampling, and their personal dose monitoring results and health examination information were retrospectively analyzed to determine the factors affecting thyroid abnormalities. Results The M (P₂₅, P₇₅) of thyroid absorbed dose (D_T) was 1.55 (0.65, 3.96) mGy in the 1657 investigated workers. The attribute-specific medians of D_T were 1.29, 1.38, 1.99, and 3.51 mGy for departments of diagnostic radiology, interventional radiology, radiotherapy, and nuclear medicine, respectively; and 1.10, 1.55, and 1.80 mGy for job titles of nurse, technician, and physician, respectively. Differences in D_T by gender, age, years of radiological work, age of radiation exposure onset, occupational category, and job title were statistically significant (Z=−6.35, H=708.52, 918.20, 31.19, 95.64, 39.28, P<0.05). The positive rate of thyroid abnormalities in investigated workers was 46.53% (771/1657). Among them, the positive rate of abnormal thyroid function was 22.87% (379/1657), that of abnormal thyroid morphology was 33.98% (563/1657), and that of thyroid nodule was 26.55% (440/1657). The differences in thyroid abnormality rates by gender, age, years of radiation work, age of radiation exposure onset, D_T, and job title of radiation workers were statistically significant (χ²=51.89, 49.64, 20.54, 18.29, 12.07, 16.16, P<0.05). The differences in abnormal thyroid function positive rate by gender, age of radiation exposure onset, and job title were statistically significant (χ²=26.21, 6.21, 8.32, P<0.05). The differences in the positive rates of abnormal thyroid morphology and nodules were statistically significant by gender, age, years of radiological work, age of radiation exposure onset, D_T, and job title (abnormal thyroid morphology, χ²=40.24, 64.17, 37.63, 15.17, 19.28, 15.05; nodules, χ²=31.41, 77.98, 42.11, 19.16, 21.70, 13.52, P<0.05). The positive rates of thyroid abnormality, thyroid morphology abnormality, and nodules all showed a linear increasing trend with increasing age, years of radiation work, and age of radiation exposure onset (P<0.05). The results of logistic regression analysis indicated that the factors influencing thyroid abnormalities were female (OR=2.17, 95%CI: 1.72-2.74), increased years of radiological work (OR=1.04, 95%CI: 1.03-1.06), onset of radiation exposure in age groups of 30-34 and ≥35 years (OR=1.63, 95%CI: 1.12-2.37; OR=2.58, 95%CI: 1.74-3.29), and working in department of diagnostic radiology (OR=1.40, 95%CI: 1.07-1.84). Conclusion Long-term exposure to low doses of ionizing radiation has an effect on thyroid abnormalities in medical radiation workers. Among them, being female, physicians, and working in department of diagnostic radiology are at a higher risk of abnormal thyroid function; being female, increased years of radiation work, and radiation exposure onset at age ≥30 years are associated with a higher risk of reporting abnormal thyroid morphology.

Environmental endocrine disruptors (EDCs) are ubiquitous in the environment, and detectable amounts are found in humans worldwide. EDCs can interact with nuclear receptors such as estrogen receptor, which could interfere with the normal function of endocrine system, and further cause the pathological alterations in the tissues. This article summarizes several common types of EDCs in the environment, which caused cardiac function abnormalities, and morphological growth malformations in heart as well as its relevant mechanisms, including oxidative stress, inflammatory response, changes in signal transduction, expressions of transcriptional regulatory factors, which are related to cardiac development, receptor pathways and cell apoptosis etc., for the purpose of understanding the process of EDCs-induced cardiac developmental toxicity, and further providing scientific theoretical basis for figuring out the toxicity mechanism of EDCs and the prevention and treatment of cardiac diseases.

Environmental endocrine disruptors (EDCs) are ubiquitous in the environment, and detectable amounts are found in humans worldwide. EDCs can interact with nuclear receptors such as estrogen receptor, which could interfere with the normal function of endocrine system, and further cause the pathological alterations in the tissues. This article summarizes several common types of EDCs in the environment, which caused cardiac function abnormalities, and morphological growth malformations in heart as well as its relevant mechanisms, including oxidative stress, inflammatory response, changes in signal transduction, expressions of transcriptional regulatory factors, which are related to cardiac development, receptor pathways and cell apoptosis etc., for the purpose of understanding the process of EDCs-induced cardiac developmental toxicity, and further providing scientific theoretical basis for figuring out the toxicity mechanism of EDCs and the prevention and treatment of cardiac diseases.