Resolution of anti-LGI1-associated autoimmune encephalitis in a patient after treatment with efgartigimod.

BACKGROUND: Anti leucine-rich, glioma inactivated 1 (LGI1) antibody-associated autoimmune encephalitis (AE) is the second most common AE, where the trafficking and recycling of the pathogenic immunoglobulin (IgG) can be controlled by the neonatal crystallizable fragment receptor (FcRn), making the latter as a candidate therapeutic target. Efgartigimod is an antagonist of FcRn, its ability to increase the degradation of IgGs and improve the health and quality of life of patients. ADAPT trail indicated its rapid efficacy and safety on myasthenia gravis. However, there is currently no case reported using efgartigimod for the treatment of anti-LGI1-associated AE. CASE DESCRIPTION: The patient presented with five episodes of generalized tonic-clonic seizures in the past 2 weeks. The patient had no abnormal signs on magnetic resonance imaging. Electroencephalogram examinations showed an increase in bilateral symmetric or asymmetric slow activity, without any clear epileptic waves. The cerebrospinal fluid (CSF) examination results indicated a slight increase in protein (47 mg/dL). The anti-LGI1 antibody titer in serum was 1:100 and that in CSF was 1:3.2. The treatment with intravenous methylprednisolone 1000 mg once a day combined with levetiracetam tablets failed to completely control the patient's seizures. Thus, 10 mg/kg efgartigimod was administered intravenously once a week for 2 weeks. After 2 weeks of treatment, serum levels of anti-LGI1 antibody and IgG decreased and the patient's epilepsy did not recur in the next 3 months. CONCLUSIONS: This is the first case report of using efgartigimod to treat anti-LGI1-associated AE. The combination of efgartigimod and methylprednisolone resulted in favorable outcomes, indicating that this is an optional treatment plan.

Evaluating the OpenAI's GPT-3.5 Turbo's performance in extracting information from scientific articles on diabetic retinopathy.

We aimed to compare the concordance of information extracted and the time taken between a large language model (OpenAI's GPT-3.5 Turbo via API) against conventional human extraction methods in retrieving information from scientific articles on diabetic retinopathy (DR). The extraction was done using GPT3.5 Turbo as of October 2023. OpenAI's GPT-3.5 Turbo significantly reduced the time taken for extraction. Concordance was highest at 100% for the extraction of the country of study, 64.7% for significant risk factors of DR, 47.1% for exclusion and inclusion criteria, and lastly 41.2% for odds ratio (OR) and 95% confidence interval (CI). The concordance levels seemed to indicate the complexity associated with each prompt. This suggests that OpenAI's GPT-3.5 Turbo may be adopted to extract simple information that is easily located in the text, leaving more complex information to be extracted by the researcher. It is crucial to note that the foundation model is constantly improving significantly with new versions being released quickly. Subsequent work can focus on retrieval-augmented generation (RAG), embedding, chunking PDF into useful sections, and prompting to improve the accuracy of extraction.

Synergistic Effect of Asphaltene, Resin, and Wax Improving the Emulsification and Interfacial Properties of a High-Phase-Inversion Thin Oil.

Nowadays, high-phase-inversion in situ emulsification technology has shown great potential in enhancing oil recovery from high-water-cut thin-oil reservoirs. However, emulsification characteristics, interfacial properties, and the mechanism of high phase inversion have not been systematically described. In this study, an emulsification experiment was conducted to investigate the effects of shear time, shear rate, and temperature on the phase inversion of thin oil. Furthermore, the influence of resin and wax on the dispersion of asphaltene was studied through microscopic morphology analysis. Interfacial tension measurement and interfacial viscoelasticity analysis were carried out to determine the interaction characteristics of asphaltene, resin, and wax at the interface. The results showed that, at 50 °C, the phase-inversion point of thin oil reached as high as 75%, and even at 60 °C, it remained at 70%. The shear time and shear rate did not affect the phase-inversion point of thin oil, while an increase in temperature led to a decrease in the phase-inversion point. Moreover, compared to the 20% phase-inversion point of base oil, the phase-inversion point increased with different proportions of asphaltene, resin, and wax. Particularly, at the ratio of asphaltene/resin/wax = 1:5:9, the phase-inversion point reached as high as 80%, indicating the optimal state. In this proportion, asphaltene aggregates exhibited the smallest and most uniform size, best dispersion, lower interfacial tension, and higher interfacial modulus. These findings provide reference and guidance for further enhancing oil recovery in medium-to-high-water-cut thin-oil reservoirs.

Selection and application of aptamers for p-hydroxybenzyl hydrogen sulfite after Gastrodia elata Bl. fumigated with sulfur.

Gastrodia elata Bl. is a widely used traditional Chinese medicine known for its medicinal properties. However, during the drying process, G. elata is often fumigated with sulfur to prevent corrosion and improve its appearance. Sulfur-fumigation can result in a reduction in the effective components of the herb and can also be hazardous to human health due to the remaining sulfur dioxide. Sulfur-fumigation of G. elata poses a significant challenge to both end-users and researchers. The detection of p-hydroxybenzyl hydrogen sulfite (p-HS) is a useful tool in determining whether G. elata has been fumigated with sulfur. Unfortunately, the current method for detecting p-HS is costly and requires sophisticated instruments. Therefore, there is a need to develop a more cost-effective and user-friendly method for the detection of p-HS. This study utilized the Capture-SELEX technique to screen high-affinity aptamers for p-HS, which were subsequently characterized by isothermal titration calorimetry (ITC). An aptamer sequence (seq 6) with a high affinity of Kd = 26.5 µM was obtained following 8 rounds of selection against p-HS. With the aptamer serving as the recognition element and gold nanoparticles as the colorimetric indicator, a simple and efficient colorimetric sensor was developed for the specific detection of p-HS. This detection method exhibited a limit of detection of 1 µg/ml, while the p-HS recoveries demonstrated a range of between 88.5 % and 105 % for samples of G. elata obtained in the market. In summary, the aptamer exhibited a high affinity for p-HS, and the sensor developed through the use of a colloidal gold detector based on nucleic acid aptamer can be utilized for rapid detection of sulfur-fumigated G. elata. With these findings, this research paper provides valuable scientific insights and highlights significant potential for future studies in this area.

Prognostic Factors of Mortality in Nonchronic Obstructive Pulmonary Disease Chronic Lung Disease: A Scoping Review.

Introduction: Patients with chronic lung disease (CLD) experience a heavy symptom burden at the end of life, but their uptake of palliative care is notably low. Having an understanding of a patient's prognosis would facilitate shared decision making on treatment options and care planning between patients, families, and their clinicians, and complement clinicians' assessments of patients' unmet palliative needs. While literature on prognostication in patients with chronic obstructive pulmonary disease (COPD) has been established and summarized, information for other CLDs remains less consolidated. Summarizing the mortality risk factors for non-COPD CLDs would be a novel contribution to literature. Hence, we aimed to identify and summarize the prognostic factors associated with non-COPD CLDs from the literature. Methods: We conducted a scoping review following published guidelines. We searched MEDLINE, Embase, PubMed, CINAHL, Cochrane Library, and Web of Science for studies published between 2000 and 2020 that described non-COPD CLD populations with an all-cause mortality risk period of up to three years. Only primary studies which reported associations with mortality adjusted through multivariable analysis were included. Results: Fifty-five studies were reviewed, with 53 based on interstitial lung disease (ILD) or connective tissue disease-associated ILD populations and two in bronchiectasis populations. Prognostic factors were classified into 10 domains, with pulmonary function and disease being the largest. Older age, lower forced vital capacity, and lower carbon monoxide diffusing capacity were most commonly investigated and associated with statistically significant increases in mortality risks. Conclusions: This comprehensive overview of prognostic factors for patients with non-COPD CLDs would facilitate the identification and prioritization of candidate factors to predict short-term mortality, supporting tool development for decision making and to identify high-risk patients for palliative needs assessments. Literature focused on patients with ILDs, and more studies should be conducted on other CLDs to bridge the knowledge gap.

Erratum: A novel selective AKR1C3-activated prodrug AST-3424/OBI-3424 exhibits broad anti-tumor activity.

[This corrects the article on p. 3645 in vol. 11, PMID: 34354865.].

Perceived Roles and Barriers in Delivering Community-Based Care: A Qualitative Study of Health and Social Care Professionals.

Introduction: As healthcare systems increasingly embrace population health management, the integration of health and social care to improve the health and well-being of individuals is crucial. Thus, we conducted a qualitative study in Singapore to understand health and social care professionals' (HCPs and SCPs) perception of the roles they played in delivering community-based care. Methods: A descriptive phenomenological research design was adopted. HCPs and SCPs (n = 53) providing services in community settings were recruited purposefully and interviewed through eleven focus group discussions. Each session was recorded and transcribed. Thematic analysis was applied. Results: Our results revealed eight themes in three main categories describing the roles played by HCPs and SCPs, including: (1) delivering needs-based care in community settings; (2) activating and empowering clients in health care, and (3) fostering community-based sustainable support networks. Six barriers encountered while performing these roles were also identified. Discussion and Conclusion: Our results highlight that the roles of HCPs and SCPs go beyond the provision of direct medical and social care. They were involved in activating and empowering clients to take care of their health, and importantly, fostering community-based sustainable support networks to better empower individuals in coping with health challenges. The identified barriers shed light on areas for potential improvements for integrated community care.

Virulence Characteristics and Drug Resistance of the Prevalent Capsule Types in Acinetobacter baumannii.

Acinetobacter baumannii is a highly antibiotic-resistant pathogen causing nosocomial severe life-threatening infections, especially in critically ill patients. Capsular polysaccharide is a major virulence factor of A. baumannii both in vitro and in vivo. In this study, 220 isolates were collected in the hospital. The prevalent capsular types of A. baumannii were determined using polymerase chain reaction, and the clinical characteristics of infections were analyzed. The virulence of these strains was determined by serum-killing resistance, biofilm formation, and Galleria mellonella survival assays. Twenty-eight isolates (12.7%) carried KL2, and 22 isolates (10%) carried the types KL10, KL14, KL22, and KL52. Compared with non-KL2 (KL10, KL14, KL22, and KL52) isolates, KL2 isolates had significantly higher resistance to all antimicrobials except tigecycline, cefoperazone-sulbactam, or colistin. Seventy-five percent of KL2 A. baumannii and 72.7% of non-KL2 were highly virulent using a G. mellonella model. Biofilm formation was significantly different between the KL2 and non-KL2 groups. The biofilm production of non-KL2 A. baumannii was significantly stronger than that of KL2 A. baumannii. These findings highlight the role of KL2 as a powerful factor for drug resistance and virulence of A. baumannii.

Risk factors for incident falls in Singaporean community-dwelling adult men and women: a prospective cohort study.

OBJECTIVES: Our study aimed to identify the risk factors of incident falls between men and women. DESIGN: Prospective cohort study. SETTING: The study recruited participants from the Central region of Singapore. Baseline and follow-up data were collected via a face-to-face survey. PARTICIPANTS: Community-dwelling adults aged 40 years and above from the Population Health Index Survey. OUTCOME MEASURE: Incident falls were defined as the experience of a fall between the baseline and 1-year follow-up but having no falls 1 year prior to baseline. Multiple logistic regressions were performed to determine the association of sociodemographic factors, medical history and lifestyle with incident falls. Sex subgroup analyses were conducted to examine sex-specific risk factors for incident falls. RESULTS: 1056 participants were included in the analysis. At 1-year follow-up, 9.6% of the participants experienced an incident fall. Incidence of falls in women was 9.8% compared with 7.4% in men. In the multivariable analysis for the overall sample, older age (OR: 1.88, 95% CI: 1.10 to 2.86), being pre-frail (OR: 2.13, 95% CI: 1.12 to 4.00) and having depression or feeling depressed/anxious (OR: 2.35, 95% CI: 1.10 to 4.99) were associated with higher odds for incident falls. In subgroup analyses, older age was a risk factor for incident falls in men (OR: 2.68, 95% CI: 1.21 to 5.90) and pre-frail was a risk factor for incident falls in women (OR: 2.82, 95% CI: 1.28 to 6.20). There was no significant interaction effect between sex and age group (p value=0.341) and sex and frailty status (p value=0.181). CONCLUSION: Older age, presence of pre-frailty and having depression or feeling depressed/anxious were associated with higher odds of incident falls. In our subgroup analyses, older age was a risk factor for incident falls in men and being pre-frail was a risk factor for incident falls in women. These findings provide useful information for community health services in designing falls prevention programmes for community-dwelling adults in a multi-ethnic Asian population.

Immunogenicity of a spike protein subunit-based COVID-19 vaccine with broad protection against various SARS-CoV-2 variants in animal studies.

SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need. In this study, we developed a protein-based vaccine BCVax that is consisted of antigen delta strain spike protein and QS21-based adjuvant AB801 in nanoparticle immune stimulation complex format (AB801-ISCOM). Results from animal studies showed that high level of anti-S protein IgG was induced after two doses of BCVax and the IgG was capable of neutralizing multiple variants of pseudovirus including omicron BA.1 or BA.2 strains. In addition, strong Th1 response was stimulated after BCVax immunization. Furthermore, BCvax with AB801-ISCOM as the adjuvant showed significant stronger immunity compared with the vaccine using aluminum hydroxide plus CpG 1018 as the adjuvant. BCVax was also evaluated as a booster after two prior vaccinations, the IgG titers and pseudovirus neutralization activities against BA.2 or BA.4/BA.5 were further enhanced suggesting BCVax is a promising candidate as booster. Taken together, the pre-clinical data warrant BCVax for further development in clinic.

The variants of polymyxin susceptibility in different species of genus Aeromonas.

The aquatic environment is an important medium for the accumulation and dissemination of antibiotic-resistant bacteria as it is often closely related to human activities. Previous studies paid little attention to the prevalence and mechanism of polymyxin-resistant bacteria in the aquatic environment. As a Gram-negative opportunistic pathogen widely distributed in aquatic ecosystems, the antibiotic-resistant profile of Aeromonas spp. deserves much attention. In this study, we identified 61 Aeromonas spp. isolates from water samples in the section of the Yangtze River. The total polymyxin B (PMB) resistance rate of these strains was 49.18% (30/61), showing a high level of polymyxin resistance in Aeromonas spp. The MIC50 and MIC90 for PMB exhibited a significant discrepancy among different species (p < 0.001). The MIC50 and MIC90 for PMB in the Aeromonas hydrophila were 128 mg/L and above 128 mg/L while in Aeromonas caviae and Aeromonas veronii, the MIC50 and MIC90 value were both 2 mg/L. Only two A. veronii strains (MIC = 2 mg/L) and one A. caviae strain (MIC = 0.5 mg/L) were identified as carrying mobilized polymyxin resistant gene mcr-3.42, and mcr-3.16. All mcr genes were located in the chromosome. This is the first report that the downstream region of mcr-3.42 was the truncated mcr-3-like gene separated by the insertion sequences of ISAs20 (1,674 bp) and ISAs2 (1,084 bp). Analysis of epidemiology of mcr-positive Aeromonas genomes from GenBank database showed that the genus Aeromonas and the aquatic environment might be the potential container and reservoir of mcr-3. By the whole-genome sequencing and qRT-PCR, we inferred that the sequence differences in the AAA domain of MlaF protein and its expression level among these three species might be involved in the development of polymyxin resistance. Our study provided evidences of the possible mechanism for the variety of polymyxin susceptibility in different species of the genus Aeromonas and a theoretical basis for the surveillance of the aquatic environment.

Identification and Analysis of Small Molecule Inhibitors of CRISPR-Cas9 in Human Cells.

Genome editing tools based on CRISPR-Cas systems can repair genetic mutations in situ; however, off-target effects and DNA damage lesions that result from genome editing remain major roadblocks to its full clinical implementation. Protein and chemical inhibitors of CRISPR-Cas systems may reduce off-target effects and DNA damage. Here we describe the identification of several lead chemical inhibitors that could specifically inhibit the activity of Streptococcus pyogenes Cas9 (SpCas9). In addition, we obtained derivatives of lead inhibitors that could penetrate the cell membrane and inhibit SpCas9 in cellulo. Two of these compounds, SP2 and SP24, were able to improve the specificity of SpCas9 in cellulo at low-micromolar concentration. Furthermore, microscale thermophoresis (MST) assays showed that SP24 might inhibit SpCas9 activity by interacting with both the SpCas9 protein and the SpCas9-gRNA ribonucleoprotein complex. Taken together, SP24 is a novel chemical inhibitor of SpCas9 which has the potential to enhance therapies that utilize SpCas9.

Acute Necrotizing Pancreatitis Complicated by Multiple Splanchnic Venous Thromboses and Bilateral Renal Infarctions in a Patient With Recent COVID-19 Infection: A Case Report.

Splanchnic vein thrombosis (SVT) is a well-known complication of pancreatitis, but extra-splanchnic thrombosis is rarely seen. We report a case of acute necrotizing pancreatitis complicated by portal vein thrombosis and resultant hepatic infarction, splenic vein thrombosis, bilateral renal infarction, and bowel hypoperfusion in an 81-year-old man with recent coronavirus disease 2019 (COVID-19) infection. To the best of our knowledge, this is the first documented case of such extensive intra-abdominal thromboses complicating severe acute pancreatitis. Despite multi-organ support and systemic anticoagulation, he deteriorated into multiple organ failure and died after 72 hours. He had no prior history of thrombotic disorders. COVID-19 infection can cause sustained prothrombotic changes, while severe acute pancreatitis also produces an inflammatory response that promotes coagulation. Together, the two concurrent disease processes may have resulted in the particularly extensive intra-abdominal thromboses and infarctions seen in this patient. Physicians should be mindful of the elevated risk of severe vascular complications in acute pancreatitis patients with concurrent or recent COVID-19 infection.

Does povidone-iodine application in surgical procedures help in the prevention of surgical site infections? An updated meta-analysis.

Introduction: Surgical site infections (SSIs) occur after an operative procedure and can range from superficial to deep wound infections. The World Health Organization (WHO) and the Centers for Disease Control (CDC) have proposed guidelines recommending measures to prevent SSIs. Intraoperative measures are largely focused on decontamination of the skin and intraoperative wound irrigation using soap and antiseptics and are simple, efficient, and cost-effective measures to reduce SSIs. Povidone-iodine (PVI) is a topical antiseptic widely used for the reduction of SSIs. Aim: A meta-analysis was conducted to determine the efficacy of preoperative or intraoperative use of PVI from randomized controlled trials (RCTs). Material and methods: A systematic literature review was conducted using MEDLINE and Central databases for RCTs that involved PVI application versus saline or no treatment control groups across various surgical categories. The primary outcome was SSI or post-operative wound infections. A random-effects model was used to calculate the pooled risk ratio and subgroup analyses were performed. Results: A total of 59 RCTs were included in the meta-analysis with information from 20,497 patients. A reduction in overall SSI incidence was found (RR = 0.70, 0.60-0.80, p = 0.0002, I2 = 44%). Subgroup analyses showed that the comparator treatment and type of procedure did not modify the effect of PVI on SSI incidence. However, inconsistent results on SSI incidence were obtained when the data were stratified by PVI application method and surgery category. Conclusions: The results of the meta-analysis provide support for the preoperative or intraoperative use of PVI in decreasing the incidence of SSI.

Emergence of Colistin Resistance Gene mcr-10 in Enterobacterales Isolates Recovered from Fecal Samples of Chickens, Slaughterhouse Workers, and a Nearby Resident.

The wide spread of plasmid-borne mobilized colistin resistance (mcr) genes from animals to humans broadly challenges the clinical use of polymyxins. Here, we evaluated the incidence of a recently reported mcr variant, mcr-10, in animals and humans in the same area. Our results revealed the presence of novel mcr-10-carrying plasmids in two Klebsiella pneumoniae isolates from chickens, one Escherichia coli isolate from slaughterhouse workers, and a chromosome-borne mcr-10 gene in Enterobacter kobei from a healthy resident in the same region. It is worth mentioning that the multidrug-resistant ST11 K. pneumoniae isolates coharboring mcr-10 and mcr-8 genes in two separate plasmids not only were resistant to polymyxins (MIC = 8 mg/L) but also showed reduced susceptibility to tigecycline (MIC ≥ 2 mg/L) due to the tet(A) mutation or the tmexCD1-toprJ1 gene cluster. The structure xerC-mcr10-insCinsD-like was found in genetic environments of both the plasmid and chromosome carrying mcr-10. We compared genomic epidemiological characteristics of mcr-10-harboring bacteria available in 941,449 genomes in the NCBI database (including strains of K. pneumoniae, E. coli, and E. kobei) with isolates in this study. The results indicated a sporadic distribution of mcr-10 all around the world and in a variety of sources, including humans, environments, and animals, which confirms that mcr-10 has spread among various hosts and warrants close monitoring and further future studies. IMPORTANCE We discovered mcr-10-harboring isolates in the "one health" approach and reported for the first time multidrug-resistant clinically threatening ST11 K. pneumoniae isolates coharboring mcr-10 and mcr-8 genes that are resistant to polymyxins and show reduced susceptibility to tigecycline. The exhaustive screening of 941,449 bacterial genomes in the GenBank database discovered a sporadic distribution of mcr-10-harboring isolates all around the world in a variety of sources, especially humans, which warrants close monitoring and a particular concern in clinical settings.

Functional Irreplaceability of Escherichia coli and Shewanella oneidensis OxyRs Is Critically Determined by Intrinsic Differences in Oligomerization.

LysR-type transcriptional regulators (LTTRs), which function in diverse biological processes in prokaryotes, are composed of a conserved structure with an N-terminal DNA-binding domain (DBD) and a C-terminal signal-sensing regulatory domain (RD). LTTRs that sense and respond to the same signal are often functionally exchangeable in bacterial species across wide phyla, but this phenomenon has not been demonstrated for the H2O2-sensing and -responding OxyRs. Here, we systematically examined the biochemical and structural determinants differentiating activator-only OxyRs from dual-activity ones by comparing OxyRs from two Gammaproteobacteria, Escherichia coli and Shewanella oneidensis. Our data show that EcOxyR could function as neither an activator nor a repressor in S. oneidensis. Using SoOxyR-based OxyR chimeras and mutants, we demonstrated that residues 283 to 289, which form the first half of the last C-terminal α-helix (α10), are critical for the proper function of SoOxyR and cannot be replaced with the EcOxyR counterpart. Crystal structural analysis reveals that α10 is important for the oligomerization of SoOxyR, which, unlike EcOxyR, forms several high-order oligomers upon DNA binding. As the mechanisms of OxyR oligomerization vary substantially among bacterial species, our findings underscore the importance of subtle structural features in determining regulatory activities of structurally similar proteins descending from a common ancestor. IMPORTANCE Evolution may drive homologous proteins to be functionally nonexchangeable in different organisms. However, much is unknown about the mechanisms underlying this phenomenon beyond amino acid substitutions. Here, we systematically examined the biochemical and structural determinants differentiating functionally nonexchangeable OxyRs, H2O2-responding transcriptional regulators from two Gammaproteobacteria, Escherichia coli and Shewanella oneidensis. Using SoOxyR-based OxyR chimeras and mutants, we demonstrated that residues 283 to 289, which form the first half of the last C-terminal α-helix (α10), are critical for the proper function of SoOxyR and cannot be replaced with the EcOxyR counterpart. Crystal structural analysis reveals that this last helix is critical for formation of high-order oligomers upon DNA binding, a phenomenon not observed with EcOxyR. Our findings provide a new dimension to differences in sequence and structural features among bacterial species in determining regulatory activities of homologous regulators.

Association Between Angiotensin-Converting Enzyme Gene I/D Polymorphism and Polycystic Ovary Syndrome Susceptibility: a Meta-analysis.

Rec ent studies have suggested a closer association between angiotensin-converting enzyme (ACE) gene polymorphisms and polycystic ovary syndrome (PCOS) risk, but the results were inconsistent. We conducted this meta-analysis to explore the precise associations between ACE gene I/D polymorphism and PCOS risk. Online electronic databases (PubMed, Embase, SCI index, CNKI, and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the association between ACE gene I/D polymorphism and PCOS risk. In addition, heterogeneity, accumulative/sensitivity analysis, and publication bias were conducted to check the statistical power. Overall, 12 published case-control studies with 2248 patients and 1759 controls were included according to the criteria. Significant increased risk was found for PCOS susceptibility with I/D mutation (D vs. I: OR = 1.62, 95%CI = 1.24-2.11, P < 0.01, I2 = 86.1%; DD vs. II: OR = 2.10, 95%CI = 1.35-3.27, P < 0.01, I2 = 79.8%; ID + DD vs. II: OR = 1.57, 95%CI = 1.06-2.32, P = 0.02, I2 = 79.3%; DD vs. II + ID: OR = 1.91, 95%CI = 1.39-2.65, P < 0.01, I2 = 79.1%). Furthermore, some similar associations were also observed in subgroups. In summary, the current evidences indicated that ACE gene I/D polymorphism plays an important role in PCOS development, both in Asian and Caucasian descendants.

Evaluate how steaming and sulfur fumigation change the microstructure, physicochemical properties and in vitro digestibility of Gastrodia elata Bl. starch.

The sulfur dioxide gas (SO2) generated by sulfur burning can improve the appearance quality of food and enhance the storage time. However, excessive sulfur dioxide will pollute the environment and cause deterioration of food quality, and even the high residual levels can increase the risk of cancer. As Gastrodia elata Blume is prone to corruption during processing, sulfur fumigation is often used for preservation. In this study, spectral analysis and Texture Profile Analysis (TPA) were used to investigate the effects of traditional sulfur fumigation processing on the morphology quality, edible quality and structural characteristics of G. elata. The results showed that compared with direct drying, the pH decreased by 0.399 of the sulfur fumigated after steamed treatment G. elata, and the morphology quality, pasting ability and gel edible quality of the starch were significantly improved. In addition, it was suggested that sulfur fumigation after steaming could promote the release of molecular chains from starch granules and thus enhance the cross-linking between molecules, which explained the reason for the improve of starch edible quality. This study can provide technical and theoretical support for improving the quality of starch rich foods, replacing sulfur fumigation and reducing potential environmental hazards.

A novel selective AKR1C3-activated prodrug AST-3424/OBI-3424 exhibits broad anti-tumor activity.

AST-3424/OBI-3424 (denoted by 3424) is a novel prodrug bis-alkylating agent activated by AKR1C3. AKR1C3 is overexpressed in many types of cancer, particularly in liver, non-small cell lung, gastric, renal and CRPC cancer. Currently 3424 is being studied in phase 1/2 clinical trials for the treatment of solid and hematologic cancers, and it represents potentially a novel, selective anti-cancer agent for multiple indications. In this study, AKR1C3-dependent activation of 3424 was investigated in vitro using recombinant human AKR1C3. AKR1C3-dependent cytotoxicity of 3424 was determined in a wide range of human cancer cell lines with different AKR1C3 expression levels. In addition, anti-tumor activity of 3424 was also investigated in a broad panel of CDX and PDX models. AKR1C3-dependent activation of prodrug 3424 was evident by monitoring the decrease of 3424 and generation of the active form, 2660. Kinetic analysis indicated that AKR1C3 exhibited higher catalytic efficiency towards 3424 compared to the physiological substrates. There was a strong correlation between 3424 cytotoxic potency and AKR1C3 expression. The racemic mixture induced DNA cross-linking in a concentration dependent manner. Tumor growth inhibition of 3424 was shown to be better than or comparable to the standard of care chemotherapy at clinically achievable doses as a single agent in various CDX models with high expression of AKR1C3, including liver HepG2, lung H460, castration-resistant prostate VCaP, gastric SNU-16, and kidney A498 cancer cell lines. The excellent anti-tumor efficacy of 3424 was further demonstrated in PDX models which have high level of AKR1C3 expression, but not in a model with low level of AKR1C3 expression. In the combination therapy, we showed that 3424 could enhance the efficacy of the standard care of chemotherapy in the CDX models. The results described here highlight that 3424 exhibits AKR1C3-dependent cytotoxicity in vitro and anti-tumor activity in vivo in a wide range of human cancer types, which support further development of 3424 as an anti-cancer agent for treating different types of cancers and the use of AKR1C3 as a biomarker to profile cancer patients and further guide patient selection for therapy with 3424.

MMP-10 rs17435959 Polymorphism is Associated with the Formation and Stability of Carotid Atherosclerosis Plaque: A Case-Control Study.

BACKGROUND: Matrix metalloproteinase 10 (MMP-10) has a close relationship with carotid atherosclerosis (CAS) and cerebral infarction. The MMP-10 rs17435959 polymorphism causes a leucine to valine transition at codon 4 in exon 1 of the MMP-10 gene and may have functional effects. OBJECTIVES: To investigate the relationship between the MMP-10 rs17435959 polymorphism and the formation and stability of CAS plaques. MATERIALS AND METHODS: The present case-control study contains 738 visitors who came to our health examination center for the first time. According to the carotid ultrasound examinations, visitors were classified into the vulnerable plaque group (41-86 years old, 141 male, 105 female), the stable plaque group (41-86 years old, 141 male, 105 female) and the no plaque group (41-85 years old, 141 male, 105 female). All visitors in the three groups were sex- and- age-matched, and cardiovascular and cerebrovascular diseases were absent. The polymorphism was genotyped by real-time polymerase chain reaction- restriction. RESULTS: Compared to the GG genotype, the frequency of the CC and CG genotypes was significantly more common in the vulnerable plaque group than in the no plaque group (18.7% vs. 7.7%, unadjusted P = 0.002). Moreover, compared to the G allele, the frequency of the C allele was significantly more common in the vulnerable plaque group than in the no plaque group (10.4% vs. 3.9%, unadjusted P = 0.000) and in the vulnerable plaque group than in the stable plaque group (10.4% vs. 5.1%, unadjusted P = 0.008). Binary logistic regression showed that the CC and CG genotype was independent risk factor for the formation (P = 0.019, OR = 1.961, 95% CI [1.117, 3.444]) and vulnerability (P = 0.035, OR = 1.842, 95% CI [1.045, 3.247]) of CAS plaques. Moreover, individuals who have the C allele showed a higher level of fibrinogen, which was an independent risk factor for the formation of CAS plaques (P = 0.000, OR = 2.425, 95% CI [1.475, 3.985]). CONCLUSIONS: The rs17435959 polymorphism was associated with the formation and vulnerability of CAS plaques. Individuals who had variant-type MMP-10 showed higher levels of fibrinogen, which promoted the formation of CAS plaques.