Mass Spectrometry Imaging Combined with Sparse Autoencoder Method Reveals Altered Phosphorylcholine Distribution in Imipramine Treated Wild-Type Mice Brains.

Mass spectrometry imaging (MSI) is essential for visualizing drug distribution, metabolites, and significant biomolecules in pharmacokinetic studies. This study mainly focuses on imipramine, a tricyclic antidepressant that affects endogenous metabolite concentrations. The aim was to use atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI)-MSI combined with different dimensionality reduction methods to examine the distribution and impact of imipramine on endogenous metabolites in the brains of treated wild-type mice. Brain sections from both control and imipramine-treated mice underwent AP-MALDI-MSI. Dimensionality reduction methods, including principal component analysis, multivariate curve resolution, and sparse autoencoder (SAE), were employed to extract valuable information from the MSI data. Only the SAE method identified phosphorylcholine (ChoP) as a potential marker distinguishing between the control and treated mice brains. Additionally, a significant decrease in ChoP accumulation was observed in the cerebellum, hypothalamus, thalamus, midbrain, caudate putamen, and striatum ventral regions of the treated mice brains. The application of dimensionality reduction methods, particularly the SAE method, to the AP-MALDI-MSI data is a novel approach for peak selection in AP-MALDI-MSI data analysis. This study revealed a significant decrease in ChoP in imipramine-treated mice brains.

Oral behaviors and anxiety are significant predictors of jaw function limitation in patients with anterior disc displacement without reduction.

OBJECTIVE: We aimed to describe jaw function characteristics in patients with anterior disc displacement without reduction (ADDWoR) using the jaw function limitation scale (JFLS), and to investigate the effects of biopsychosocial risk factors on limited jaw function. DESIGN: In this cross-sectional study of 636 patients with ADDWoR (females, 568; males, 68), we used the JFLS to assess jaw function. Behavioral, psychological, sociodemographic, and biomedical data were collected. Multivariate logistic regression analysis was used to determine risk factors affecting limited jaw function. A receiver operating characteristic curve was used to evaluate the predictive effect of these risk factors. RESULTS: ADDWoR-associated limitations included restricted jaw mobility and mastication, which exceeded median global functional limitations scale scores, especially mouth opening to bite an apple and chewing tough food. Females had greater limitations in jaw mobility, verbal and emotional communication, and overall. Multivariate logistic regression analysis findings indicated that oral behaviors, anxiety, sex, pain intensity, and maximal mouth opening (MMO) were predictive of limited jaw function (area under the curve, 72 %). CONCLUSION: Patients with ADDWoR reported mastication and jaw mobility restrictions, with females having more pronounced limitations, and specific risk factors identified as significant predictors of jaw function limitations. Along with pain relief and improvement in MMO, appropriate psychological counseling and oral behavioral correction facilitates recovery of jaw function in such patients.

Granting analysis of the credit financing of the platform-type highway transportation supply chain.

Against the background of digital development, this study's research object is the platform-based highway transportation supply chain. It also analyzes two modes of supply chain financial credit financing, namely, upstream, and downstream enterprises of the platform, and network freight platform as the main financing body. Notably, the financial provider sets up a transaction credit based on the principle of business truth, and closed-loop transactions, determine the upper limit of the credit line based on the principle of financing self-compensation, build the expected profit maximization model, and establish the optimal credit line. Combined with the Highway Freight Index and Logistics Prosperity Index, the dynamic early warning value is established for the financing mode, where the platform as the main financing body. Through numerical analysis, the credit line and expected profit increase with the transaction credit, expected freight volume, and credit interest rate under the two modes, and the increase deriving from the credit interest rate is more significant. Finally, this paper describes the two-dimensional credit matrix of the financing subject via transaction credit and credit interest rate, which provides an intuitive credit reference for financial institutions to conduct the credit financing of the platform-based highway transportation supply chain.

Simultaneous ST-elevation in lead augmented vector right (aVR) and III in non-ST-elevation acute coronary syndromes.

Background: The value of ST-elevation in lead augmented vector right (aVR) remains controversial in clinical practice. This study aimed to investigate the association of simultaneous ST-elevation in lead aVR and III with angiographic findings and clinical outcomes in patients with non-ST-elevation acute coronary syndromes (NSTEACS). Methods: In this observational study, patients who had been diagnosed with NSTEACS and presented with ST-elevation in lead aVR and without ST-elevation in any other two contiguous leads were enrolled from January 2018 to June 2019. Demographic, baseline clinical, angiographic and interventional characteristics as well as clinical outcomes were collected and recorded on standardized case report forms. Results: A total of 157 patients meeting the criteria were finally enrolled in this study and classified into two groups according to the presence of ST-elevation in lead III. Patients in the two groups were similar in average age and previous history of hypertension, diabetes mellitus, hyperlipidemia, chronic kidney disease, stroke, and peripheral vascular diseases (all P>0.05). Patients with ST-elevation in lead III tended to present with myocardial hypertrophy in the echocardiography (P=0.02). The cases with ST-elevation in lead III showed higher high sensitivity troponin T (hs-TnT; P=0.08) and creatinine kinase MB isoenzyme (CK-MB; P<0.01) whereas those without ST-elevation in lead III showed higher N-terminal pro brain natriuretic peptide (NT-proBNP; P=0.02). Of note, patients with ST-elevation in lead III presented with more ST-depression in multiple leads [especially in lead I, augmented vector left (aVL), V3-V6] as well as higher degree of ST-depression (all P<0.05) and were more likely to develop multi-vessel and left main trunk (LM) lesions (P=0.04), with 20% of the cases having a LM lesion and 60% having triple vessel lesions. Patients with ST-elevation in lead III were at increased risk of 3-year major adverse cardiovascular events (MACEs), despite no significant statistical difference between the two groups (hazard ratio =1.29; P=0.26). Conclusions: The NSTEACS cases with simultaneous ST-elevation in lead III and aVR tended to present with more multiple leads with ST-depression, higher degree of ST-depression, and more LM or multi-vessel lesions, suggesting a broader range of severe myocardial ischemia. The concurrent presentation of ST-elevation in lead III and aVR may play a vital role in the diagnosis, risk-stratification, and prediction of poor prognosis during the management of NSTEACS patients.

Distribution and transformation of potentially toxic elements in cracks under coal mining disturbance in farmland.

The ground cracks resulting from coal mining activities induce alterations in the physical and chemical characteristics of soil. However, limited knowledge exists regarding the impact of subsidence caused by coal mining on the distribution of potentially toxic elements (PTEs) fractions in farmland soil. In this study, we collected 19 soil profiles at varying depths from the soil surface and at horizontal distances of 0, 1, 2, and 5 m from the vertical crack. Using BCR extraction fractionation, we determined the geochemical fractions and total concentrations of Chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd) and lead (Pb) to investigate their ecological risk, spatial fraction distribution, and main influencing factors. Results showed that the E r i values of Cd appearing in 68.7% of the samples were higher than 40 and less than 80, presented a moderate ecological risk. Chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), and lead (Pb) were mainly bound to residual fractions (> 60%) with lower mobility and Cd was dominated by F1 (acid-soluble fractions, 50%) and F2 (reducible fractions, 29%) in surface soil (0-20 cm). The geochemical fractionation revealed that the mobile fractions (F1-acid-soluble and F2-reducible) of PTEs were primarily located near the crack, influenced by available potassium. In contrast, the less mobile fractions (F3-oxidizable and F4-residual) exhibited higher concentrations at distances of 2 and 5 m from the crack, except for arsenic, influenced by the presence of clay particles and available phosphorus.

Analysis of an adult diabetes mellitus caused by a rare mutation of the gene: A case report.

BACKGROUND: This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence, featuring a unique mutation in the peroxisome proliferator-activated receptor gamma (PPARG) gene. Data Access Statement: Research data supporting this publication are available from the NN repository at www.NNN.org/download/. CASE SUMMARY: The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family members. Additionally, high-throughput sequencing was conducted to analyze the PPARG genes of the patient, her siblings, and their offspring. The results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy, accompanied by insulin resistance and hypertriglyceridemia. Furthermore, these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation patterns. The results from the gene detection process demonstrated a heterozygous mutation of guanine (G) at position 284 in the coding region of exon 2 of PPARG, which replaced the base adenine (A) (exon2c.284A>Gp.Tyr95Cys). This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated protein. Notably, both of her siblings harbored a nucleotide heterozygous variation at the same site, and both were diagnosed with diabetes. CONCLUSION: The PPARG gene mutation, particularly the p.Tyr95Cys mutation, may represent a newly identified subtype of maturity-onset diabetes of the young. This subtype is characterized by insulin resistance and lipid metabolism disorders.

Reactivity-matched synthesis of monodisperse Ag(In,Ga)S2 QDs with efficient luminescence.

I-III-VI quantum dots (QDs) have gained widespread attention owing to their significant advantages of non-toxicity, large structural tolerance, and efficient photoluminescence potential. However, the disbalance of reactivity between the elements will result in undesired products and compromised optical properties. Reducing the activity of highly reactive group IB elements is the most common approach, but it will reduce the overall reactivity and lead to a wide dispersion of QD sizes. In this study, we propose a method to improve the overall reactivity of the reaction system using the highly active IIIA precursor InI3, which triggers rapid nucleation and promotes the formation of Ag(In,Ga)S2 (AIGS) QDs, resulting in monodisperse particle size distributions and a significantly improved photoluminescence quantum yield (PLQY) (from 12% to 72%). Furthermore, narrow band edge emission is realized by coating a gallium sulfide (GaSx) shell on the basis of obtaining high-quality AIGS QDs. The core/shell QDs exhibit a 90% PLQY with a full width at half maximum (FWHM) of only 31 nm at 530 nm. This study provides a viable design strategy to synthesize monodisperse AIGS QDs with a narrow peak width and efficient luminescence, promoting the application of AIGS QDs in the field of luminescent displays.

Potential SARS-CoV-2 Mpro steroid inhibitors from Aphanamixis polystachya (Wall.) R. N. Parker.

Herein, six previously undescribed steroids (1-6), were isolated from leaves and twigs of Aphanamixis polystachya (Wall.) R. N. Parker (Meliaceae). Their structures were elucidated by comprehensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR, UV, and IR. Antiviral activity of these compounds were evaluated. Compounds 1-6 showed varying degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 200 µM.

Transformation of antibiotics to non-toxic and non-bactericidal products by laccases ensure the safety of Stropharia rugosoannulata.

The substantial use of antibiotics contributes to the spread and evolution of antibiotic resistance, posing potential risks to food production systems, including mushroom production. In this study, the potential risk of antibiotics to Stropharia rugosoannulata, the third most productive straw-rotting mushroom in China, was assessed, and the underlying mechanisms were investigated. Tetracycline exposure at environmentally relevant concentrations (<500 µg/L) did not influence the growth of S. rugosoannulata mycelia, while high concentrations of tetracycline (>500 mg/L) slightly inhibited its growth. Biodegradation was identified as the main antibiotic removal mechanism in S. rugosoannulata, with a degradation rate reaching 98.31 % at 200 mg/L tetracycline. High antibiotic removal efficiency was observed with secreted proteins of S. rugosoannulata, showing removal efficiency in the order of tetracyclines > sulfadiazines > quinolones. Antibiotic degradation products lost the ability to inhibit the growth of Escherichia coli, and tetracycline degradation products could not confer a growth advantage to antibiotic-resistant strains. Two laccases, SrLAC1 and SrLAC9, responsible for antibiotic degradation were identified based on proteomic analysis. Eleven antibiotics from tetracyclines, sulfonamides, and quinolones families could be transformed by these two laccases with degradation rates of 95.54-99.95 %, 54.43-100 %, and 5.68-57.12 %, respectively. The biosafety of the antibiotic degradation products was evaluated using the Toxicity Estimation Software Tool (TEST), revealing a decreased toxicity or no toxic effect. None of the S. rugosoannulata fruiting bodies from seven provinces in China contained detectable antibiotic-resistance genes (ARGs). This study demonstrated that S. rugosoannulata can degrade antibiotics into non-toxic and non-bactericidal products that do not accelerate the spread of antibiotic resistance, ensuring the safety of S. rugosoannulata production.

Teachers Matter More Than Sites and Facilities: Provincial-Level Educational Predictors of Adolescent Life Satisfaction.

Purpose: Life satisfaction can predict students' school engagement and academic performance, and has shown significant regional differences among adolescents. The predictive effect of economic factors as regional characteristics on adolescent life satisfaction has been extensively examined; however, the regional educational factors that could predict adolescent life satisfaction remain unknown. This study aimed to identify provincial-level educational factors that can predict adolescent life satisfaction. Methods: The participants comprised 16,737 students, aged 11-16 years (M age = 13.82; SD age = 0.77; 8767 girls, 7970 boys), from 31 provinces in China. Students completed measures on socioeconomic status and life satisfaction. Multilevel modeling was adopted in data analysis. Results: Adolescent life satisfaction was positively correlated with family socioeconomic status, and negatively associated with age and academic ranking. Life satisfaction was lower for girls than boys. Some regional education development indicators could predict adolescent life satisfaction: ratio of students to teachers, ratio of students to teachers with master's degrees, and multimedia classroom size negatively correlated with adolescent life satisfaction; meanwhile per capita sports field area positively correlated with adolescent life satisfaction. Per capita education expenditure, classroom area, laboratory area, computer room area, language lab area, gymnasium area, green space area, sports field area, computers per student, number of books, and value of equipment and instruments could not significantly predict life satisfaction in this study. Conclusion: The findings suggest that the life satisfaction of female adolescents, those in older age groups, with lower academic rankings and socioeconomic status, and those residing in regions with underdeveloped educational systems was relatively poor. These groups of adolescents should therefore be given special attention. To enhance their life satisfaction, some certain provinces should consider implementing measures such as increasing the number of teachers, reducing class sizes, and providing more opportunities for physical activity among junior middle school students.

Diagnostic performance of MRI in detecting prostate cancer in patients with prostate-specific antigen levels of 4-10 ng/mL: a systematic review and meta-analysis.

OBJECTIVE: To investigate the diagnostic performance of MRI in detecting clinically significant prostate cancer (csPCa) and prostate cancer (PCa) in patients with prostate-specific antigen (PSA) levels of 4-10 ng/mL. METHODS: A computerized search of PubMed, Embase, Cochrane Library, Medline, and Web of Science was conducted from inception until October 31, 2023. We included articles on the use of MRI to detect csPCa or PCa at 4-10 ng/mL PSA. The primary and secondary outcomes were MRI performance in csPCa and PCa detection, respectively; the estimates of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were pooled in a bivariate random-effects model. RESULTS: Among the 19 studies (3879 patients), there were 10 (2205 patients) and 13 studies (2965 patients) that reported MRI for detecting csPCa or PCa, respectively. The pooled sensitivity and specificity for csPCa detection were 0.84 (95% confidence interval [CI], 0.79-0.88) and 0.76 (95%CI, 0.65-0.84), respectively, for PCa detection were 0.82 (95%CI, 0.75-0.87) and 0.74 (95%CI, 0.65-0.82), respectively. The pooled NPV for csPCa detection was 0.91 (0.87-0.93). Biparametric magnetic resonance imaging also showed a significantly higher sensitivity and specificity relative to multiparametric magnetic resonance imaging (both p < 0.01). CONCLUSION: Prostate MRI enables the detection of csPCa and PCa with satisfactory performance in the PSA gray zone. The excellent NPV for csPCa detection indicates the possibility of biopsy decision-making in patients in the PSA gray zone, but substantial heterogeneity among the included studies should be taken into account. CLINICAL RELEVANCE STATEMENT: Prostate MRI can be considered a reliable and satisfactory tool for detecting csPCa and PCa in patients with PSA in the "gray zone", allowing for reducing unnecessary biopsy and optimizing the overall examination process. KEY POINTS: Prostate-specific antigen (PSA) is a common screening tool for prostate cancer but risks overdiagnosis. MRI demonstrated excellent negative predictive value for prostate cancer in the PSA gray zone. MRI can influence decision-making for these patients, and biparametric MRI should be further evaluated.

Highly Efficient Production of Cellulosic Ethanol from Poplar Using an Optimal C6/C5 Co-Fermentation Strain of Saccharomyces cerevisiae.

Cellulosic ethanol is the key technology to alleviate the pressure of energy supply and climate change. However, the ethanol production process, which is close to industrial production and has a high saccharification rate and ethanol yield, still needs to be developed. This study demonstrates the effective conversion of poplar wood waste into fuel-grade ethanol. By employing a two-step pretreatment using sodium chlorite (SC)-dilute sulfuric acid (DSA), the raw material achieved a sugar conversion rate exceeding 85% of the theoretical value. Under optimized conditions, brewing yeast co-utilizing C6/C5 enabled a yield of 35 g/L ethanol from 10% solid loading delignified poplar hydrolysate. We increased the solid loading to enhance the final ethanol concentration and optimized both the hydrolysis and fermentation stages. With 20% solid loading delignified poplar hydrolysate, the final ethanol concentration reached 60 g/L, a 71.4% increase from the 10% solid loading. Our work incorporates the pretreatment, enzymatic hydrolysis, and fermentation stages to establish a simple, crude poplar waste fuel ethanol process, expanding the range of feedstocks for second-generation fuel ethanol production.

Discovery and Development of NLRP3 Inhibitors Targeting the LRR Domain to Disrupt NLRP3-NEK7 Interaction for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease. Targeting NLRP3 inflammasome, specifically its interaction with NEK7 via the LRR domain of NLRP3, is a promising therapeutic strategy. Our research aimed to disrupt this interaction by focusing on the LRR domain. Through virtual screening, we identified five compounds with potent anti-inflammatory effects and ideal LRR binding affinity. Lead compound C878-1943 underwent structural optimization, yielding pyridoimidazole derivatives with different anti-inflammatory activities. Compound I-19 from the initial series effectively inhibited caspase-1 and IL-1ß release in an adjuvant-induced arthritis (AIA) rat model, significantly reducing joint swelling and spleen/thymus indices. To further enhance potency and extend in vivo half-life, a second series including II-8 was developed, demonstrating superior efficacy and longer half-life. Both I-19 and II-8 bind to the LRR domain, inhibiting NLRP3 inflammasome activation. These findings introduce novel small molecule inhibitors targeting the LRR domain of NLRP3 protein and disrupt NLRP3-NEK7 interaction, offering a novel approach for RA treatment.

APOA5 alleviates reactive oxygen species to promote oxaliplatin resistance in PIK3CA-mutated colorectal cancer.

Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic efficiency. However, there is limited research on the correlation between chemotherapy resistance and lipid metabolism, including PIK3CA mutant tumors. In this present study, we found that PIK3CA-E545K mutation attenuated cell apoptosis and increased the cell viability of CRC with L-OHP treatment in vitro and in vivo. Mechanistically, PIK3CA-E545K mutation promoted the nuclear accumulation of SREBP1, which promoted the transcription of Apolipoprotein A5 (APOA5). APOA5 activated the PPARγ signaling pathway to alleviate reactive oxygen species (ROS) production following L-OHP treatment, which contributed to cell survival of CRC cells. Moreover, APOA5 overexpression enhanced the stemness-related traits of CRC cells. Increased APOA5 expression was associated with PIK3CA mutation in tumor specimens and poor response to first-line chemotherapy, which was an independent detrimental factor for chemotherapy sensitivity in CRC patients. Taken together, this study indicated that PIK3CA-E545K mutation promoted L-OHP resistance by upregulating APOA5 transcription in CRC, which could be a potent target for improving L-OHP chemotherapeutic efficiency. Our study shed light to improve chemotherapy sensitivity through nutrient management in CRC.

Characteristics and comparative study of medicinal materials between China and India based on data mining from literatures.

ETHNOPHARMACOLOGICAL RELEVANCE: China and India have unique traditional medicine systems with vast territory and rich medical resources. Traditional medicines in China include traditional Chinese medicine, Tibetan medicine, Mongolian medicine, Uyghur medicine, Dai medicine, etc. In the third national survey of Chinese medicine resources, 12694 medicinal materials were identified. Traditional medicines in India include Ayurveda, Unani, Siddha, Homoeopathy, etc. There are 7263 medicinal materials in India. AIM OF THE STUDY: To reveal the characteristics of medicinal materials between China and India respectively, and to compare the similarities and differences in terms of properties, tastes, medicinal parts and therapeutic uses and to promote the exchange of traditional medicine between China and India and the international trade of traditional medicine industry. METHODS: The information of medicinal materials between China and India was extracted from The Chinese Traditional Medicine Resource Records and Pharmacopoeia of the People's Republic of China, as well as from 71 Indian herbal monographs. The information of each medicinal material, such as types, families, genera, properties, distribution, medicinal parts, efficacy, therapeutic uses, dosage form and dosage, was recorded in Excel for statistical analysis and visual comparison. RESULTS: A total of 12694 medicinal materials in China and 5362 medicinal materials in India were identified. The medicinal materials were mostly distributed in Southwest China and northern India. Plants were the main sources of medicinal materials. The common medicinal parts in China were whole medicinal materials, roots and rhizomes, and India used more renewable fruits, seeds and leaves. They are commonly used in the treatment of digestive system diseases. There were 1048 medicinal materials used by both China and India, which were distributed in 188 families and 685 genera. The Chinese and Indian pharmacopoeias had a total of 80 species of medicinal materials used by both China and India. CONCLUSIONS: The characteristics of medicinal materials between China and India were somewhat different, which was conducive to provide a reference basis for traditional medicine in China or India to increase the medicinal parts and indications when using a certain medicinal material, as well as to expand the source of medicine and introduce new resources. However, there were certain similarities and shared medicinal materials, which can tap the potential of bilateral trade of medicinal materials between China and India, so as to promote the medical cultural exchange and economic and trade cooperation between the two countries.

Identification and Validation of PKR as a Direct Target for the Novel Sulfonamide-Substituted Tetrahydroquinoline Nonselective Inhibitor of the NLRP3 Inflammasome.

The NLRP3 inflammasome is a critical component of the innate immune system. The persistent abnormal activation of the NLRP3 inflammasome is implicated in numerous human diseases. Herein, sulfonamide-substituted tetrahydroquinoline derivative S-9 was identified as the most promising NLRP3 inhibitor, without obvious cytotoxicity. In vitro, S-9 inhibited the priming and activation stages of the NLRP3 inflammasome. Incidentally, we also observed that S-9 had inhibitory effects on the NLRC4 and AIM2 inflammasomes. To elucidate the multiple anti-inflammatory activities of S-9, photoaffinity probe P-2, which contained a photoaffinity label and a functional handle, was developed for target identification by chemical proteomics. We identified PKR as a novel target of S-9 in addition to NLRP3 by target fishing. Furthermore, S-9 exhibited a significant anti-neuroinflammatory effect in vivo. In summary, our findings show that S-9 is a promising lead compound targeting both PKR and NLRP3 that could emerge as a molecular tool for treating inflammasome-related diseases.

Gestational diabetes mellitus is associated with distinct folate-related metabolites in early and mid-pregnancy: A prospective cohort study.

AIMS: This study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype. MATERIALS AND METHODS: A prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5-methyltetrahydrofolate (5-MTHF), 5, 10-methylene-tetrahydrofolate (5,10-CH2-THF), 5- formyltetrahydrofolate (5-CHO-THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5-MTHF, and methylmalonic acid (MMA), were determined at 6-17 weeks and 20-26 weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28 weeks of pregnancy by a 75-g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders. RESULTS: The study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI]) = 1.36 (1.01-1.84)], UMFA ≥ P90 [aOR (95% CI) = 1.82 (1.23-2.69)], and HCY ≥ P75 [aOR (95% CI) = 1.40 (1.04-1.88)] in early pregnancy, and RBC 5-MTHF [aOR (95% CI) = 1.48 (1.10-2.00)], RBC 5,10-CH2-THF [aOR (95% CI) = 1.55 (1.15-2.10)], and plasma 5-MTHF [aOR (95% CI) = 1.36 (1.00-1.86)] in mid-pregnancy ≥ P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1-h and 2-h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5- MTHF and 5,10-CH2-THF, and plasma 5- MTHF in mid-pregnancy are positively associated with the 1-h glucose level (p < 0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM. CONCLUSIONS: Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5-MTHF and 5,10-CH2-THF and plasma 5-MTHF during mid-pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM.

Effects of the Affordable Care Act Medicaid Expansions on the Employment and Work Hours of Nursing Assistants in Hospitals and Nursing Homes.

We examine the effects of the Affordable Care Act Medicaid expansions on the employment and work hours of nursing assistants (NAs). We use the 2011-2019 American Community Survey data to identify NAs likely to be affected by Medicaid expansions (income up to 138% of the federal poverty level) in nursing homes and hospitals. Using classical difference-in-differences regressions, we find that Medicaid expansions have little effect on employment and work hours among NAs in the full sample. However, there is a 4.4 percentage-point increase in the probability of working part-time (<30 hours/week) for nursing home NAs (p < .05). We found no employment effects of Medicaid expansions for hospital NAs. Our study adds to the literature on the heterogeneous effects of Medicaid expansions on work effort across occupations and workplaces. The rise in part-time employment for nursing home NAs following Medicaid expansions suggests the need for improved benefits to encourage full-time employment.

Elucidating Gender-Specific Distribution of Imipramine, Chloroquine, and Their Metabolites in Mice Kidney Tissues through AP-MALDI-MSI.

Knowledge of gender-specific drug distributions in different organs are of great importance for personalized medicine and reducing toxicity. However, such drug distributions have not been well studied. In this study, we investigated potential differences in the distribution of imipramine and chloroquine, as well as their metabolites, between male and female kidneys. Kidneys were collected from mice treated with imipramine or chloroquine and then subjected to atmospheric pressure matrix-assisted laser desorption ionization-mass spectrometry imaging (AP-MALDI-MSI). We observed differential distributions of the drugs and their metabolites between male and female kidneys. Imipramine showed prominent distributions in the cortex and medulla in male and female kidneys, respectively. Desipramine, one of the metabolites of imipramine, showed significantly higher (*** p < 0.001) distributions in the medulla of the male kidney compared to that of the female kidney. Chloroquine and its metabolites were accumulated in the pelvis of both male and female kidneys. Interestingly, they showed a characteristic distribution in the medulla of the female kidney, while almost no distributions were observed in the same areas of the male kidney. For the first time, our study revealed that the distributions of imipramine, chloroquine, and their metabolites were different in male and female kidneys.

A case report of febrile ulceronecrotic Mucha-Habermann disease.

Background: Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare and severe variant of pityriasis lichenoides et varioliformis acuta, characterized by a rapid onset of painful, necrotic skin lesions and systemic symptoms. The diagnosis of FUMHD is complex, hinging on the clinical presentation, histopathological findings, and exclusion of other severe dermatoses. The key diagnostic criteria include sudden development of ulceronecrotic papules and plaques, fever, and evidence of systemic disease. Due to the rarity of FUMHD, there is no consensus on optimal treatment, reflecting a significant gap in the dermatological practice. Case Description: This report details a multimodal approach tailored to our 13-year-old patient, incorporating systemic corticosteroids, immunosuppressive therapy, and intensive supportive care. The strategy was designed to address the acute and aggressive nature of the disease while mitigating potential systemic complications. The report emphasizes on the intricate, multi-layered care required to manage FUMHD, illustrating the challenges and considerations in treating this complex condition. It underscored the necessity of a personalized, comprehensive care plan that extends beyond medical intervention to include psychological and social support. The outcome of our patient was encouraging, with a marked reduction in cutaneous manifestations and improvement in systemic symptoms. Conclusions: It was found that prevention and care of skin injuries and complications, as well as the protection of patient's mental state during the development of the disease, are very important. Therefore, early diagnosis, prompt treatment, close monitoring of infection indicators, and specialized care are essential to improve the prognosis of patients with FUMHD.