[Clinical analysis of lung adenocarcinoma with epidermal growth factor receptor mutation transformed into sarcoma].

Objective: To analyze the clinical data of a case of lung adenocarcinoma with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) resistance transforming into sarcoma, and to conduct a literature review to improve the understanding of the resistance mechanism. Histological transformation is a unique form of acquired resistance of EGFR-TKIs in non-small cell lung cancer (NSCLC). Thereinto, the transformation of small cell carcinoma is more common, and the transformation of sarcoma is rarely reported. Methods: Clinicopathological data on the treatment process, pathological features, and clinical outcome of the patient with EGFR-TKIs-resistance lung adenocarcinoma transforming into sarcoma were collected. The literature was reviewed to analyze the pathogenetic mechanism for sarcomatoid carcinoma or sarcoma transformation after drug resistance of adenocarcinoma, as well as the clinical characteristics of the patients and the corresponding therapeutic schemes. Results: We reported a patient with lung adenocarcinoma who developed EGFR-T790M mutation after first-line treatment with icotinib and sarcoma transformation after second-line treatment with almonertinib. Chemotherapy, radioactive particle implantation, antiangiogenic therapy and immunotherapy were followed, but the results were unsatisfactory. There was no report of EGFR-TKIs-resistant lung adenocarcinoma transforming into sarcoma. Among the 14 reports of adenocarcinoma transforming into sarcomatoid carcinoma, 8 cases had EGFR mutation, 3 cases had ALK mutation, 2 cases had ROS1 mutation, and 1 case had no asscoiated sensitive mutation. The median survival of 14 patients with adenocarcinoma transforming to sarcomatoid carcinoma was only 3 months. Conclusions: Sarcoma transformation can be one of the forms of drug resistance in patients with lung adenocarcinoma with EGFR-TKIs. The prognosis of patients with adenocarcinoma after transformation into sarcoma is poor.

Analyzing the incidence of silicosis across various industries in Taiwan: a study of occupational disease surveillance by linking national-based workers' and medicoadministrative databases.

OBJECTIVES: This study aimed to establish an occupational disease surveillance system by identifying high-risk industries for silicosis in Taiwan using a national database linkage approach. METHODS: The study was based on a comprehensive analysis of benefit claims from the National Labor Insurance Research Database and medical records from the National Health Insurance Research Database between 2004 and 2020, providing coverage for more than 88.5% of the workforce and 99.9% of citizens. Silicosis was defined as having received compensation for labor insurance benefits or having received a diagnosis of silicosis (International Classification of Diseases, 10th Revision: J62 or International Classification of Diseases, Ninth Revision: 502). The study used the International Standard Industrial Classification of All Economic Activities for industry-specific classification. Cox proportional hazard models were used to compare the silicosis incidence and risk among each industry and identify high-risk industries for silicosis. RESULTS: This study analyzed 1466 cases of silicosis between 2004 and 2020 and found that 28 industries had incidence rates of over 40 cases per 100,000 workers, indicating more than double the risk of developing silicosis. Of these industries, 14 were considered high risk (relative risk of over four times). Among these, this study identified industries rarely mentioned in the past, such as wholesale of brick, sand, cement, and products, artistic creation, landscape construction, and materials recovery. Stratification by years of work experience reveals those industries such as quarrying of stone, sand, clay, and other mining, construction of buildings, landscape construction, site preparation, foundation and structure construction, building completion and finishing, manufacture of ships, boats, and floating structures, and plumbing, heat, and air conditioning installation display higher hazard ratios for individuals with <10 years of work experience. CONCLUSIONS: The current surveillance system has identified certain industries that are at a higher risk of developing silicosis, which could be used for future occupational epidemiological surveys and targeted preventive measures in these sectors.

[The association between calcium supplementation in antenatal childbearing aged women and risk of small for gestational age among neonatal singleton in Shaanxi province].

Objective: This study explored the association between antenatal calcium supplementation in the childbearing aged women and risk of small for gestational age infant (SGA) among singleton in Shaanxi province,China. Methods: Multi-stage random cluster sampling method was employed to collect information about pregnant women, who were pregnant and had definite outcomes, and their infants, from 30 districts (counties) in 2010 to 2013. Information was collected by face-to-face questionnaire survey. Generalized linear mixed models were employed after adjusting covariates. Dependent variable was whether single-birth neonate was SGA, and independent variable was calcium supplementation of childbearing aged women in different pregnant periods. Results: A total of 28 357 childbearing aged women was recruited in this study. The age of these women was (28.08±4.74) years old, of which, 79.28% were rural residents and 60.90% had calcium supplementation intake. There was a number of 12 810 female in singleton neonates. The neonatal birth weight and gestational age were (3.27±0.16) kg and (277.44±8.80) day, respectively. The prevalence of SGA was 11.35% in total, and 10.48% in mothers with maternal calcium supplementation and 12.70% in mothers without maternal calcium supplementation in whole antenatal period. There were statistically significant differences seen in antenatal calcium supplementation within the subgroups of maternal age (whether the mother was an advanced maternal woman), residential area, maternal occupation, maternal parity, maternal education level, and household incomes (P<0.05). After adjusting these covariates, the risk of SGA among childbearing aged women with antenatal calcium supplementation showed 16% decreased risk (OR=0.84, 95%CI: 0.77-0.92). Further analysis of the different antenatal periods showed that calcium supplementation during the second and third trimester had a statistically significant difference in reducing the risk of neonatal SGA (P<0.05). Besides, subgroup analysis showed that there was a statistically significant difference between the perinatal calcium supplementation and the single-born neonates with SGA Significance (P<0.05) in non-advanced women, those who had a low education level and moderate household economic status groups. Conclusion: The risk reduction of SGA among singleton neonates is related to calcium supplementation during antenatal period in Shaanxi province.

[Application of electronic data acquisition system REDCap in large natural population-based cohort studies].

Cohort study is one of the basic methods used in epidemiological research. With the development of the etiological analysis of complex diseases such as cardiovascular diseases, large natural population-based cohort study has become a popular topic in medical research. In the process of cohort development, one of the important issues is to ensure the efficiency and safety on data collection. As a database management system, with open source, free clinical research data collection and high quality, REDCap can widely be applied in large population-based cohort studies. This article summarizes the baseline survey and follow-up procedures on cohort studies and introduces a REDCap-system-based solution for data collection and management. Contents on the establishment of data working groups, data collection, cohort follow-up methods and field application are also discussed in this paper, in order to improve the efficiency of data collection and management in cohort study to help the development of cohort study in China.

[The association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age among neonatal twins in Shaanxi Province].

Objective: To explore the association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age (SGA) among neonatal twins in Shaanxi Province. Methods: From July to December 2013, a total of 30 027 childbearing aged women, who were pregnant from January 2010 to November 2013 and had definite outcomes, were selected from 30 districts (counties) of Shaanxi Province by using the multi-stage random sampling method. The questionnaires with a face-to-face survey method were used to retrospectively collect demographic information, pregnancy history, lifestyle during pregnancy, disease history, nutritional supplements, and health care during pregnancy. Information on the gestational age and birth weight of the newborn were obtained by consulting the medical certificate of birth and were registered as twin A and twin B by birth order. Finally, 356 childbearing aged women and their twin babies with complete data were included in the analysis. A generalized estimation equation model was used to analyze the association between the frequency of prenatal care and the risk of SGA among neonatal twins. Results: The age of childbearing aged women was (27.44±4.68) years old, of which 79.49% (283 women) were rural residents and 44.38% (158 women) had seven or more times prenatal care. The gestational age and birth weight were (37.64±2.51) weeks and (2 510±497) g, respectively. The prevalence of SGA was 51.40% (183/356) for twin A and 53.37% (190/356) for twin B, respectively. The prevalence of SGA was 44.30% (70/158) for twin A with seven or more times prenatal care and 42.41% (67/158) for twin B with seven or more times prenatal care, which was lower than that for twins with less than seven times prenatal care, respectively [57.07% (113/198) and 62.12% (123/198)] (P values were 0.017 and <0.001). The results of generalized estimation equation model suggested that compared to those with less than seven times prenatal care, after adjusting for parity, birth order, place of residence, maternal age, occupation, education, family wealth index, passive smoking, pregnancy-induced hypertension syndrome, folic acid, and iron supplement during perinatal period, and gender of the newborn, the OR (95%CI) of risk of SGA among childbearing aged women with seven or more times prenatal care was 0.60 (0.40-0.91). Conclusion: Seven or more times prenatal care could reduce the risk of SGA among neonatal twins in Shanxi Province.

[Association between congenital heart disease and maternal disease in early pregnancy in women of childbearing age].

Objective: To investigate the relationship between maternal disease in early pregnancy of women of childbearing age and congenital heart disease of neonates. Methods: A cross-sectional design was used in this study and stratified multistage random sampling method was used. A questionnaire survey was conducted in the childbearing-aged women during 2010-2013 in Shaanxi province. Propensity score (PS) matched (1∶1) analysis was used to match participants with diseases to those without disease in early pregnancy. Through the control of the confounders step by step, a logistic regression model was established to evaluate the ORs of congenital heart disease according to the independent variable of maternal disease. Results: A total of 28 680 pairs of mothers and infants were included in this study, the proportion of the women with disease in early pregnancy was 20.25% (5 807). After PS matching, 5 436 pairs were matched. After adjusting all confounding factors, the multivariable logistic regression analysis results showed that maternal disease (OR=1.86, 95%CI: 1.23-2.81), especially cold (OR=2.19, 95%CI: 1.46-3.28), gynecological disease (OR=4.74, 95%CI: 2.03-11.09) and diabetes (OR=14.00, 95%CI: 1.64-119.21), in early pregnancy were the risk factors for congenital heart disease of neonate. Conclusion: In women of childbearing age, disease in early pregnancy, especially cold, gynecological disease and diabetes, can increase the risk of congenital heart disease in neonates.

[Relationship between preterm birth of infant and medication during pregnancy in women of childbearing age in Shaanxi].

Objective: To understand the relationship between medication during pregnancy and single live preterm birth of infant in women of childbearing age in Shaanxi province. Methods: A cross-sectional design was used in this study and stratified multistage random sampling method was used. A questionnaire survey was conducted in the childbearing-aged women selected through multi stage stratified random sampling in Shaanxi during 2010 to 2013. Qualitative datum was described by percentage and measurement datum was described by mean±standard deviation. Logistic regression analysis was done to evaluate the relationship between medication during pregnancy and preterm birth of infant. Results: The overall incidence rate of premature birth was 2.7% in Shaanxi. Among the 28 841 mothers participating in this study, the proportion of medication use at any time during pregnancy was 15.8%, and the most commonly used drug was cold medicine (5.9%). After adjusting all confounding factors, the multivariable logistic regression analysis results showed that taking hormone medicine (OR=2.23, 95%CI: 1.19-4.18), antihypertensive medicine (OR=7.74, 95%CI: 4.28-13.95) and other medicines (OR=2.15, 95%CI: 1.60-2.89) during early pregnancy were the risk factors for preterm delivery, the risk was 2.23 times, 7.74 times and 2.15 times higher compared with those taking no these medicines. Conclusion: Using hormone medicine, antihypertensive medicine and other medicines during pregnancy increased the risk for preterm delivery in women of childbearing age in Shaanxi.

Ablation of Tacr2 in mice leads to gastric emptying disturbance.

BACKGROUND: Tacr2 is one of the G protein-coupled receptors(GPCRs) that mediate the biological actions of tachykinins. It is abundantly expressed in the gastrointestinal (GI) system and is thought to play an important role in GI motility, secretion, and visceral sensitivity. Previously, the physiological and pathophysiological functions of Tacr2 were mainly studied using Tacr2 selective agonists or antagonists. Here, we seek to investigate the effect of Tacr2 disruption in mice to provide further insights. METHODS: The Tacr2 knockout mice were generated by homologous recombination and the phenotypic changes of the Tacr2-null mice were analyzed and compared with their wild type (wt) littermates. KEY RESULTS: Increased food retention was detected in Tacr2-/- mice. The stomach of Tacr2-/- mice had thinner muscularis externa and less neurons in the myenteric plexus. The stomach and small intestine exhibited longer duration of electrical field stimulation (EFS)-induced inhibition in the gastric fundus and decreased frequency of migrating motor complex (MMC), respectively. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were significantly up-regulated due to Tarc2 deficiency, contributing to enhanced nitric oxide (NO) signaling in the stomach of Tacr2-/- mice. Intraperitoneal application of 7-nitroindazole (7-NI) to Tacr2-/- mice effectively relieved the gastric emptying disturbance. Moreover, Creb and NF-κB signalings were involved in the regulation of these physiological changes initiated by Tacr2 deficiency. CONCLUSIONS & INFERENCES: Tacr2 negatively regulated the expression of nNOS and VIP both in vivo and in vitro. Its ablation in mice elevated the expression of nNOS and VIP, enhanced NO signaling and changed the Creb and NF-κB signalings, finally leading to the gastric emptying disturbance of Tacr2-/- mice.

XBP1 promoter polymorphism modulates platinum-based chemotherapy gastrointestinal toxicity for advanced non-small cell lung cancer patients.

BACKGROUND: The X-box binding protein 1 (XBP1) is a critical transcription factor in the endoplasmic reticulum stress response, which is essential for the maintenance of cellular homeostasis. Here, we investigated whether the regulatory variant rs2269577 of the XBP1 gene influences clinical outcome in advanced non-small cell lung cancer (NSCLC) patients undergoing platinum-based chemotherapy. PATIENTS AND METHODS: We recruited 663 Chinese patients with advanced NSCLC treated with platinum-based regimens and assessed the association between rs2269577 and clinical outcome. Subsequent functional analyses, including real-time quantitative PCR and dual-luciferase assays, were performed to explore possible molecular mechanisms. RESULTS: The G/G genotype of rs2269577 was significantly associated with severe gastrointestinal toxicity compared with the homozygous C/C genotype (P=0.012, odds ratio=2.755), particularly in the female, performance status 0-1, and adenocarcinoma subgroups. No significant relevance was found between rs2269577 and treatment efficacy. In gastric epithelial cells, in vitro molecular analyses demonstrated that XBP1 mRNA expression levels decreased after treatment with cisplatin and the G allele of rs2269577 weakened the transcriptional activity of the XBP1 promoter. CONCLUSION: This is the first study to evaluate the effect of XBP1 polymorphism on severe chemotherapy-related adverse outcomes in platinum-treated advanced NSCLC patients using both pharmacogenomics and functional molecular analyses.

VCP gene variation predicts outcome of advanced non-small-cell lung cancer platinum-based chemotherapy.

Valosin-containing protein (VCP), or p97, is a member of the ATP-binding protein family, and is involved in numerous cellular events, such as, protein degradation, membrane fusion, and chaperone activity. VCP has been demonstrated playing a critical role in non-small-cell lung cancer (NSCLC) pathogenesis and progression recently. We investigated the association between VCP polymorphisms and clinical outcome in advanced NSCLC patients undergoing platinum-based chemotherapy. We recruited 663 Chinese advanced NSCLC patients who were treated with platinum-based regimens, and using their clinical data, we assessed the efficacy and side effects of their treatment. Three tag-single nucleotide polymorphisms (SNPs) of VCP were genotyped. SNP rs2074549 showed a significant association with severe neutropenia. Its G/G genotype increased the risk of grade 3 or 4 neutropenia compared with wild-type homozygotes A/A (P = .001, odds ratio = 2.975). Haplotype association analysis revealed that CGA was associated with the increased incidence of severe neutropenia (P = .041, odds ratio = 1.439). However, no significant relationship was found between the presence of VCP polymorphisms and treatment efficacy when objective response, progression-free survival, and overall survival (OS) were evaluated. Our study is the first to provide evidence that VCP polymorphisms are associated with a severe chemotherapy-related adverse outcome in platinum-treated advanced NSCLC patients.

Endoscopic management of suspected esophageal foreign body in adults.

Foreign bodies should not be allowed to remain in the esophagus beyond 24 hours after presentation. However, some patients with esophageal foreign body ingestion do not come to the hospital immediately and may delay medical intervention from the time of ingestion. The aim of this study was to investigate the outcomes of adults with suspected esophageal foreign body ingestion according to the time of ingestion and types of foreign bodies. A total of 326 adult patients (151 men and 175 women) were analyzed, and divided into two groups according to the time period: within or beyond 24 hours from ingestion to endoscopic intervention. A total of 172 patients (52.7%) were found to have ingested foreign bodies; 73.5% were removed smoothly, 10.3% were treated by push technique and 16.0% with failed retrieval received alternative treatments. A higher proportion of patients in the beyond-24 hours group suffered from odynophagia (25.9 vs. 12.9%, P < 0.05). Negative identification of esophageal foreign bodies was more frequent in the beyond-24 hours group (67 vs. 40.2%, P < 0.05), but these patients showed higher proportions of esophageal ulcers (21.1 vs. 7.2%, P < 0.05). The beyond-24 hours group also showed a significantly higher rate of foreign bodies in the lower esophagus (40.0 vs. 15.3%, P < 0.05). Patients with esophageal food bolus impaction had significant delayed endoscopic intervention, longer therapeutic endoscopic time, higher proportions of esophageal cancer, stricture and fewer complications. Endoscopic intervention within 24 hours from the time of ingestion should be considered early in adults, because delaying intervention may produce more symptomatic esophageal ulcerations with odynophagia.

Isolation and characterization of ACTX-6: a cytotoxic L-amino acid oxidase from Agkistrodon acutus snake venom.

The characterization of an L-amino acid oxidase purified from Agkistrodon acutus snake venom was investigated. An L-amino acid oxidase (LAAO) was purified from A. acutus snake venom through DEAE Sepharose F.F. and Source 30 S chromatography. The molecular mass of this enzyme was determined by SDS-PAGE, size exclusion chromatography, and mass spectrometry. Substrate specificity, cytotoxicity, antitumor activity in vivo, and apoptosis-inducing activity were assayed. The LAAO purified from A. acutus snake venom was designated as ACTX-6. It is a covalently bound homodimer and its molecular mass is about 96 kDa. This enzyme preferred to oxidize hydrophobic L-amino acids; the best substrates were L-Met, L-Leu, L-Trp, and L-Phe. ACTX-6 demonstrated cytotoxicity in vitro and could inhibit tumor growth in vivo. Flow cytometry analysis showed that it could markedly increase accumulation of sub-G1 phase, which suggested that this enzyme could induce apoptosis. ACTX-6 could effectively inhibit tumor growth and it is a potential substance to develop into an antitumor drug.

A novel index for analysing the response of a microbial culture to changes in the environmental variables during cultivation.

AIMS: To analyse the sensitivity of a microbial culture to variations in the cultivation conditions by using the motile intensity of the cells. METHODS AND RESULTS: Batch cultures of Bacillus thuringiensis were used to study the sensitivity of the cells to pulse changes in pH, temperature and oxygen supply. A droplet of the culture sample was visualized under an optical microscope and the image of the moving cells was captured with a computer controlled display camera attached to the microscope. Motile intensity was computed directly using an image analysis programme. The results showed that the different phases of cell growth exhibited different motile intensities. The motile intensity changed remarkably at the high level of the motile intensity, when the environmental variables are changed. CONCLUSIONS: The product formation was considerably reduced when a disturbance was applied at the high magnitude of motile intensity. SIGNIFICANCE AND IMPACT OF STUDY: Monitoring the motile intensity by image analysis is simple and makes it an attractive method for assessing the effect of environmental variables on the growth and product formation of microbial cultures.

Cryopreservation and biophysical properties of articular cartilage chondrocytes.

In order to successfully cryopreserve articular cartilage chondrocytes, it is important to characterize their osmotic response during the cryopreservation process, as the ice forms and the solutes concentrate. In this study, experimental work was undertaken to determine the osmotic parameters of articular cartilage chondrocytes. The osmotically inactive volume of articular cartilage chondrocytes was determined to be 44% of the isotonic volume. The membrane hydraulic conductivity parameters for water were determined by fitting a theoretical water transport model to the experimentally obtained volumetric shrinkage data; the membrane hydraulic conductivity parameter L(Pg) was found to be 0.0633 microm/min/atm, and the activation energy E, 8.23 kcal/mol. The simulated cooling process, using the osmotic parameters obtained in this study, suggests a cooling rate of 80 degrees C/min for the cryopreservation of the articular cartilage chondrocytes of hogs. The data obtained in this study could serve as a starting point for those interested in cryopreservation of chondrocytes from articular cartilage in other species in which there is clinical interest and there are no parameters for prediction of responses.

Repeated-batch production of kojic acid in a cell-retention fermenter using Aspergillus oryzae M3B9.

A cell-retention fermenter was used for the pilot-scale production of kojic acid using an improved strain of Aspergillus oryzae in repeated-batch fermentations. Among the various carbon and nitrogen sources used, sucrose and yeast extract promoted pellet morphology of fungi and higher kojic acid production. Repeated-batch culture using a medium replacement ratio of 75% gave a productivity of 5.3 gL(-1)day(-1) after 11.5 days of cultivation. While batch culture in shake-flasks resulted in a productivity of 5.1 gL(-1)day(-1), a productivity of 5 gL(-1)day(-1) was obtained in a pilot-scale fermenter. By converting the batch culture into repeated batches, the non-productive downtime of cleaning, filling and sterilizing the fermenter between each batch were eliminated, thereby increasing the kojic acid productivity.

Fed-batch culture of Bacillus thuringiensis based on motile intensity.

The operation of a fed-batch culture is more complicated than that of batch or continuous culture. Thus, an appropriate feeding strategy for fed-batch cultures should be carefully designed. In this study, a simple feeding strategy for fed-batch culture of Bacillus thuringiensis based on "motile intensity" is described. The feeding strategy consisted of two steps: (1) initiating feeding at the peak of motile intensity; (2) terminating feeding at low motile intensity (or non-motility) of the cells. In addition, the motile intensity of B. thuringiensis was used to determine the optimum environmental conditions (pH, temperature, and dissolved oxygen) and optimum medium composition. Using this fed-batch strategy, the production of thuringiensin increased 34% compared with batch culture using the same environmental conditions and medium composition. The proposed strategy for fed-batch culture helps to avoid overfeeding of substrate and facilitates on-line control. A comparison of several alternative strategies for fed-batch culture demonstrated that strategies such as glucose-stat and DO-stat result in a lower productivity than that obtained using the motility intensity method.

High-level expression of a lacZ gene from a bacterial artificial chromosome in Escherichia coli.

The GlnAP2 element has been proved to be an effective and inducible-by exogenous acetate-promoter in Escherichia coli with glnL/pta double mutations. Based on this feature, a single-copy expression vector was constructed via coupling of the glnAP2 promoter-regulated T7 RNA polymerase gene and the T7-promoter-controlled lacZ gene on a bacterial artificial chromosome. After induction with 20 mM potassium acetate, the glnL/pta double mutant E. coli harboring the single-copy plasmid produced 47,500 Miller units of beta-galactosidase activity. This high level expression, corresponding to 27% of total cell protein, was comparable to that determined with the commercial multi-copy expression vector, pET-14b, in strain E. coli Tuner (DE3) (64,300 Miller units, 41% of total cell protein). Moreover, this single-copy expression vector could be maintained for at least 150 generations even in the presence of inducers. In contrast, the multi-copy expression vector was extensively lost after induction. The results indicate that the single-copy expression system has the potential for high-level heterologous protein production for industrial applications.

Retroperitoneal subpancreatic ectopic pregnancy following in vitro fertilization in a patient with previous bilateral salpingectomy: how did it get there?

An unusual case of retroperitoneal ectopic pregnancy is reported. The patient, a 34 year old nulligravida, underwent IVF/ET following bilateral salpingectomy. A small, degenerating, intrauterine gestational sac suggested failing intrauterine pregnancy. There was no intraperitoneal free fluid. On Day 41 after ET, the patient was hospitalized because of acute epigastric pains. A pseudocyst of the head of pancreas was demonstrated by CT scan. A day later, exploratory laparotomy, because of a precipitous drop in the hemoglobin, revealed a massive retroperitoneal hematoma and an embryo in the gestational sac attached to the head of pancreas and major blood vessels. The patient did well following surgery. The mechanisms of retroperitoneal embryo migration are discussed and literature is reviewed.

Effect of shear stress on cultivation of Bacillus thuringiensis for thuringiensin production.

Cultivation of Bacillus thuringiensis for thuringiensin production is a mixed-growth-associated system. Cultivation conditions should be different during the cell growth stage and production stage. In this study, agitation speed and aeration rate were varied during the exponential growth phase and stationary phase in order to investigate the effect of shear stress via agitation on cultivation of B. thuringiensis for thuringiensin production. It was found that shear stress had a significant effect on thuringiensin production during the stationary phase. By decreasing the agitation speed during the stationary phase, product formation was increased up to 43%.

A combined solid-state and submerged cultivation integrated with adsorptive product extraction for production of Monascus red pigments.

A process taking advantages of combined solid-state and submerged cultivation of Monascus for red pigment production and integration of a product removal unit was developed. The solid-state cultivation was carried out in a 5 l fermentor, with rice being used not only as the substrate but also the support for Monascus. The inclusion of rice submergence and integration of product separation were achieved by intermittently rinsing the rice with monosodium glutamate (MSG) solutions every 12 h followed by an adsorptive extraction of the red pigment dissolved in the rinsing solution. With this new process, the Monascus red pigment production was increased by 24% as compared with that by the plain fixed-bed cultivation.