Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles.

JOURNAL/nrgr/04.03/01300535-202504000-00028/figure1/v/2024-07-06T104127Z/r/image-tiff The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration. However, it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains. This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals. Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin. Recently, we showed that the PINK1 kinase is selectively expressed as a truncated form (PINK1-55) in the primate brain. In the present study, we used multiple antibodies, including our recently developed monoclonal anti-PINK1, to validate the selective expression of PINK1 in the primate brain. We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages, which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains. PINK1 was enriched in the membrane-bound fractionations, whereas Parkin was soluble with a distinguishable distribution. Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes, though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress. These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

Release characteristics of arsenic from sediments and its source or sink competition with phosphorus: A case of a great lake with grass-algae alternation.

The arsenic (As) release from sediments in great lakes is affected by various factors. In this study, the characteristics of As release from sediments was investigated, and the As sources and sinks with the strengths in sediments from different areas (grass-type, algae-type, and grass-algae alternation areas) in great shallow lakes (Taihu Lake, China) were analyzed, and the influence of P competition in the process of As release was also studied. The results showed that changing trend of the values of equilibrium As concentration in sediments were consistent with the regional changes (0 to 28.12 µg/L), and the sediments from algae-type areas had the higher values. The sediments from western lake and northwest lake bay were a strong As and a weak P source, and the north lake bay had the opposite trend of these two regions. Intense P source competition with As from the sediments occurred in algae-type areas. The grass-type areas had strong As and P retention capacities, indicating a sink role of sediment with high As and P sorption capacities. The degree of As and P saturation had similar trend in sediments, and the grass-type areas had the higher values, 18.3%-21.4% and 15.31%-20.34%, respectively. Contribution analysis results showed that most of As release contribution was from the bottom (30-50 cm) sediments, and the surface (0-10 cm) sediments from algae-type areas contributed more to the overlying water than other region.

Characterization, expression and functional analysis of Hsp40 during LPS challenge in Blood parrot Amphilophus citrinellus ×Vieja melanura.

Heat shock protein 40 belonging to heat shock protein family plays an important role in the immune responses of organisms. In this study, the full length cDNA of Hsp40 was 2426 bp including a 1368 bp open reading frame (ORF) encoding 455 amino acids with a molecular weight of 49.16 kDa and a theoretical isoelectric point of 9.34 in blood parrot Vieja synspila ♀×Amphilophus citrinellus ♂, an important ornamental fish in China. It had three conserved domains DnaJ, CRR and DnaJ_C. Phylogenetic analysis showed that the sequence of Hsp40 among species was conserved, and the blood parrot Hsp40 was closely related to Neolamprologus brichardi. Blood parrot Hsp40 mRNA could be detected in all of the tissues examined and mainly distributed in the cytoplasm. The expression of Hsp40 was upregulated during lipopolysaccharide (LPS) challenge. Upregulated Hsp40 inhibited the activity of nuclear factor κB (NF-κB) and activated protein 1 (AP-1) and reduced the ratio of Bax/Bcl-2 mRNA expression. This study provides a theoretical basis for further exploring the role of Hsp40 gene in the anti-bacterial immunity of blood parrot.

Recent Advances in Phenazine Natural Products: Biosynthesis and Metabolic Engineering.

Phenazine natural products are a class of nitrogen-containing heterocyclic compounds produced by microorganisms. The tricyclic ring molecules show various chemical structures and extensive pharmacological activities, such as antimicrobial, anticancer, antiparasitic, anti-inflammatory, and insecticidal activities, with low toxicity to the environment. Since phenazine-1-carboxylic acid has been developed as a registered biopesticide, the application of phenazine natural products will be promising in the field of agriculture pathogenic fungi control based on broad-spectrum antifungal activity, minimal toxicity to the environment, and improvement of crop production. Currently, there are still plenty of intriguing hidden biosynthetic pathways of phenazine natural products to be discovered, and the titer of naturally occurring phenazine natural products is insufficient for agricultural applications. In this review, we spotlight the progress regarding biosynthesis and metabolic engineering research of phenazine natural products in the past decade. The review provides useful insights concerning phenazine natural products production and more clues on new phenazine derivatives biosynthesis.

Efficient metal free organic radical scintillators.

The development of high-performance metal-free organic X-ray scintillators (OXSTs), characterized by a synergistic combination of robust X-ray absorption, efficient exciton utilization, and short luminescence lifetimes, poses a considerable challenge. Here we present an effective strategy for achieving augmented X-ray scintillation through the utilization of halogenated open-shell organic radical scintillators. Our experimental results demonstrate that the synthesized scintillators exhibit strong X-ray absorption derived from halogen atoms, display efficacious X-ray stability, and theoretically achieve 100% exciton utilization efficiency with a short lifetime (∼18 ns) due to spin-allowed doublet transitions. The superior X-ray scintillation performance exhibited by these organic radicals is not only exploitable in X-ray radiography for contrast imaging of various objects but also applicable in a medical high-resolution micro-computer-tomography system for the clear visualization of fibrous veins within a bamboo stick. Our study substantiates the promise of organic radicals as prospective candidates for OXSTs, offering valuable insights and a roadmap for the development of advanced organic radical scintillators geared towards achieving high-quality X-ray radiography.

Sphk1 regulates HMGB1 via HDAC4 and mediates epithelial pyroptosis in allergic rhinitis.

Background: Allergic rhinitis (AR) is a global health issue affecting millions of individuals worldwide. Pyroptosis has emerged as a major player in the development of AR, and targeting its inhibition with specific drugs holds promise for AR treatment. However, a comprehensive understanding of the precise mechanisms underlying pyroptosis in AR remains to be explored, warranting further investigation. Objective: This study aims to elucidate the roles of HMGB1, Sphk1, and HDAC4 in regulating human nasal epithelial cell (hNEC) pyroptosis and AR. Methods: An in vitro AR cell culture model and an in vivo AR mouse model were established. Western blot, ELISA, histological staining, and flow cytometry were utilized to confirm the gene and protein expression. The interactions among Sphk1, HDAC4, and HMGB1 were validated through ChIP, Co-IP, and Dual-luciferase assay. Results and conclusion: We identified that the expression levels of Sphk1, HMGB1, and inflammasome components, including IL-18, and IL-1ß were elevated in AR patients and mouse models. Knockdown of Sphk1 inhibited hNEC pyroptosis induced by dust mite allergen. Overexpression of HDAC4 suppressed HMGB1-mediated pyroptosis in hNECs. In addition, HDAC4 was found to mediate the transcriptional regulation of HMGB1 via MEF2C, a transcription factor. Additionally, Sphk1 was shown to interact with CaMKII-δ, promoting the phosphorylation of HDAC4 and inhibiting its cytoplasmic translocation. Knockdown of HDAC4 reversed the effect of Sphk1 knockdown on pyroptosis. These discoveries offer a glimpse into the molecular mechanisms underlying AR and suggest potential therapeutic targets for the treatment of this condition.

Development of a breastfeeding co-parenting intervention program for couples with primiparas: a program development process study.

BACKGROUND: The exclusive breastfeeding rates is low in some countries. Low breastfeeding rates results in higher healthcare expenses and adverse health outcomes for individuals and society. Co-parenting is effective in promoting breastfeeding as it involves shared responsibility and collaboration between parents in raising children. However, the current breastfeeding co-parenting intervention programs exhibits significant variations in components, timing, and duration across studies. An evidence-based breastfeeding co-parenting intervention program is essential for enhancing breastfeeding-related outcomes. OBJECTIVE: To develop an evidence-based breastfeeding co-parenting intervention program for healthcare providers to guide parents with primiparas on breastfeeding. METHOD: To form an initial version of the intervention program, a systematic literature review was conducted to consolidate information on current intervention programs. Two rounds of Delphi method were followed to gather expert comments for the program modification to establish the formal version. RESULTS: Fourteen articles published between 1995 and 2022 were screened. Details of these researches, including starting and ending time, duration and specific contents, were integrated to developed the initial program. Then, six experts completed the two rounds consultation with a positive coefficient of 85.71%, coefficient judgment basis of 0.93, familiarity coefficient of 0.87, authority coefficient of 0.90 and the Kendall's W of 0.62. Finally, an evidence-based breastfeeding co-parenting intervention program was constructed in this study, consisting of breastfeeding co-parenting courses, individual counselling and a father's support group. CONCLUSION: This research developed a breastfeeding co-parenting intervention program for healthcare providers to guide primiparous parents to improve breastfeeding rates. Through a systematic literature review and Delphi method with good reliability, the program integrates breastfeeding courses, individual counseling, and a father's support group. Future research will focus on evaluating its impact and scalability to benefit maternal and infant health globally. TRIAL REGISTRATION: ChiCTR.org.cn (ChiCTR2300069648). Registration date: 2023-03-22.

Adebrelimab plus chemotherapy and sequential thoracic radiotherapy as first-line therapy for extensive-stage small-cell lung cancer (ES-SCLC): a phase II trial.

Background: This phase II prospective trial aimed to investigate the efficacy and safety of adebrelimab (PD-L1 antibody) plus first-line chemotherapy followed by sequential thoracic radiotherapy (TRT) combined with adebrelimab in extensive-stage small-cell lung cancer (ES-SCLC). Biomarkers associated with potential therapeutic effects were also explored. Methods: Patients with previously untreated ES-SCLC were enrolled at Shandong Cancer Hospital and Institute (Jinan, China). Patients received 4-6 cycles of adebrelimab (20 mg/kg, D1, Q3W) combined with EP/EC (etoposide, 100 mg/m2, D1-3, Q3W and cisplatin, 75 mg/m2, D1, Q3W or carboplatin, AUC = 5, D1, Q3W). Then patients with response sequentially underwent consolidative TRT (≥30 Gy in 10 fractions or ≥50 Gy in 25 fractions, involved-field irradiation), and maintenance adebrelimab until disease progression or intolerable adverse events (AEs). The primary endpoint was overall survival (OS). Genomic and circulating tumour DNA (ctDNA) profiling were also analyzed with tumour tissues and peripheral blood. This trial was registered with ClinicalTrials.gov, NCT04562337. Findings: From October 2020 to April 2023, 67 patients diagnosed with ES-SCLC were enrolled and received at least one dose of study treatment. All patients were included in the efficacy and safety analyses. 45 patients received sequential TRT as planned. The median OS and progression-free survival (PFS) was 21.4 months (95% CI: 17.2-not reached months) and 10.1 months (95% CI: 6.9-15.5 months), respectively. The confirmed objective response rate was 71.6% (48/67, 95% CI: 59.3-82.0%) and disease control rate was 89.6% (60/67, 95% CI: 79.7-95.7%). There were no treatment-related deaths. The most common grade 3 or higher treatment-related adverse events (TRAEs) were hematological toxicities. The incidence of any grade and G3+ pneumonitis was 25% (17/67) and 6% (4/67), respectively. No unexpected adverse events were observed. Patients without co-mutations of TP53/RB1 in both tissue and peripheral blood displayed longer PFS (tissue, P = 0.071; ctDNA, P = 0.060) and OS (tissue, P = 0.032; ctDNA, P = 0.031). Interpretation: Adebrelimab plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. Funding: This study was funded by the National Natural Science Foundation of China (82172865), Jiangsu Hengrui Pharmaceuticals Co., Ltd. and Amoy Diagnostics Co., Ltd.

Estimating expected years of life lost of psychiatric disorders in Taiwan: A Nationwide cohort study.

OBJECTIVES: This study employed a national longitudinal cohort to assess expected years of life lost (EYLL) in newly diagnosed psychiatric patients. METHODS: Data from Taiwan's National Death Registry and Health Insurance Research Database were scrutinized to identify patients with various psychiatric disorders. Disorders were ranked hierarchically, and age groups were categorized as young, middle-aged, and older adults. We utilized the semiparametric survival extrapolation method to estimate life expectancy (LE) and EYLL. Modifying effect of comorbid conditions and socioeconomic characteristics were also explored. RESULTS: Among the 5,757,431 cases, young adults with dementia, alcohol use disorder, schizophrenia, and bipolar disorder experienced an excess of 15 years of EYLL. Middle-aged adults faced approximately 9 years or more of EYLL, while older adults had lower EYLL values. Comorbid conditions, low income levels, and living in rural areas were associated with higher EYLL. CONCLUSIONS: This study underscores the substantial EYLL among young adults with psychiatric disorders and the significant impact of specific disorders on EYLL. Early intervention, tailored support, and healthcare system readiness are imperative for improved outcomes. Resource allocation and targeted interventions focusing on early detection and comprehensive treatment can alleviate the economic burden.

Chloroplast ATP synthase restricts photosynthesis under fluctuating light in tomato but not in maize.

Photosynthesis in fluctuating light requires coordinated adjustments of diffusion conductance and biochemical capacity, but the role of chloroplast ATP synthase activity (gH+) in dynamic photosynthesis is not well understood. In this study, we measured gas exchange, chlorophyll fluorescence and electrochromic shift signals in fluctuating light for leaves of tomato (Solanum lycopersicum) and maize (Zea mays). During the transition from sun to shade, simultaneous increases in gH+, effective quantum yield of PSII, and net CO2 assimilation rate (AN) occurred in tomato but uncoupled in maize, indicating that gH + limited AN during the sun-to-shade transition in tomato but not in maize. During the shade-to-sun transition, gH + increased simultaneously with stomatal conductance, mesophyll conductance and Rubisco carboxylation capacity in tomato, suggesting that gH+ is an overlooked factor affecting light induction of AN in tomato. By comparison, gH + maintained at high levels in maize and its AN was mainly restricted by stomatal conductance. Our results reveal that the kinetics of gH+ in fluctuating light differs between species, and chloroplast ATP synthase may be a potential target for improving dynamic photosynthesis in crops such as tomato.

Deterministic responses of biodiversity to climate change through exotic species invasions.

Biodiversity is increasingly threatened by local extinction under global climate change. This may reflect direct effects of climate on poorly adapted native species or increased impacts of exotic species in these conditions, but their relative importance is poorly understood. By examining global occurrence records of 142 plant species found in the Yangtze River Valley, we found that the climatic niches of exotic species differed from those of natives, mainly reflecting exotics being most common in warmer, drier and more isothermal climates in their native ranges. These differences in climatic niches, especially temperature, predicted invasion intensity in 459 plots along a 1,800-km transect in the Yangtze River Valley. On the basis of this strong match between model predictions and field survey results, we predict that invasions will probably be more intense in future climatic conditions, especially from warming at the coldest sites. The direct negative effect of warming on native diversity was larger than the indirect effects mediated through increased invasions. However, moderate invasion increased communities' overall species diversity. More broadly, our study highlights the role of exotic species in the ecological response of regional biodiversity to global climate change.

Phylogeny and evolution of hemipteran insects based on expanded genomic and transcriptomic data.

BACKGROUND: Hemiptera is the fifth species-rich order of insects and the most species-rich order of hemimetabolous insects, including numerous insect species that are of agricultural or medical significance. Despite much effort and recent advance in inferring the Hemiptera phylogeny, some high-level relationships among superfamilies remain controversial. RESULTS: We sequenced the genomes of 64 hemipteran species from 15 superfamilies and the transcriptomes of two additional scale insect species, integrating them with existing genomic and transcriptomic data to conduct a comprehensive phylogenetic analysis of Hemiptera. Our datasets comprise an average of 1625 nuclear loci of 315 species across 27 superfamilies of Hemiptera. Our analyses supported Cicadoidea and Cercopoidea as sister groups, with Membracoidea typically positioned as the sister to Cicadoidea + Cercopoidea. In most analyses, Aleyrodoidea was recovered as the sister group of all other Sternorrhyncha. A sister-group relationship was supported between Coccoidea and Aphidoidea + Phylloxeroidea. These relationships were further supported by four-cluster likelihood mapping analyses across diverse datasets. Our ancestral state reconstruction indicates phytophagy as the primary feeding strategy for Hemiptera as a whole. However, predation likely represents an ancestral state for Heteroptera, with several phytophagous lineages having evolved from predatory ancestors. Certain lineages, like Lygaeoidea, have undergone a reversal transition from phytophagy to predation. Our divergence time estimation placed the diversification of hemipterans to be between 60 and 150 million years ago. CONCLUSIONS: By expanding phylogenomic taxon sampling, we clarified the superfamily relationships within the infraorder Cicadomorpha. Our phylogenetic analyses supported the sister-group relationship between the superfamilies Cicadoidea and Cercopoidea, and the superfamily Membracoidea as the sister to Cicadoidea + Cercopoidea. Our divergence time estimation supported the close association of hemipteran diversification with the evolutionary success and adaptive radiation of angiosperms during the Cretaceous period.

Capturing subjective cognitive decline with a new combined index in low education patients with Parkinson's disease.

Objectives: Subjective Cognitive Decline (SCD) refers to self-reported cognitive decline with normal global cognition. This study aimed to capture SCD among low educated patients with Parkinson's disease (PD) using a newly established indicator. Methods: We recruited 64 PD patients with low education levels (education ≤12 years) for the study. The presence of SCD was determined based on a Unified Parkinson's Disease Rating Scale Part I (1.1) score ≥ 1. Spearman analysis and multivariate binary logistic regression analyses were conducted to investigate factors associated with the PD-SCD group. The receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the new combined index. Results: The prevalence of SCD in PD patients was 43.75%. Low educated PD-SCD patients had higher scores on the Non-Motor Symptoms Scale (NMSS), Parkinson's Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), as well as higher scores on the UPDRS-I and UPDRS-II, compared to PD patients without SCD. They also demonstrated poorer performance on the Montreal Cognitive Assessment (MoCA), particularly in the domains of executive abilities/attention/language. Multivariate binary regression confirmed the significant association between PD-SCD and MoCA-executive abilities/attention/language. Based on these findings, a combined index was established by summing the scores of MoCA-executive abilities, MoCA-attention, and MoCA-language. ROC analysis showed that the combined index could differentiate PD-SCD patients with an area under the curve (AUC) of 0.876. A score of 12 or less on the combined index had a sensitivity of 73.9% and a specificity of 76.2% for diagnosing PD-SCD. Conclusion: These low education patients with PD-SCD may exhibit potential PD-related pathological changes. It is important for clinicians to identify PD-SCD patients as early as possible. The newly combined index can help capture these low educated PD-SCD patients, with an AUC of 0.867, and is expected to assist clinicians in earlier identification and better management of PD patients.

Controlled Fabrication of Unimolecular Micelles as Versatile Nanoplatform for Multifunctional Applications.

Unimolecular micelles (UMs) are nano-sized structures that are composed of single molecules with precise composition. Compared to self-assembled polymeric micelles, UMs possess ultra-stable property even in complex biological environment. With the development of controllable polymerization and coupling chemistry, the preparation of narrowly monodispersed UMs with precise morphology and size has been realized, which further facilitates their multifunctional applications. After brief introduction, state-of-the-art advances in the synthesis and applications of UMs are discussed with an emphasis on their bioapplications. It is believed that these UMs have great potential in future fabrication of multifunctional nanoplatforms.

ImmunoPET imaging of EpCAM in solid tumours with nanobody tracers: a preclinical study.

PURPOSE: Epithelial cell adhesion molecule (EpCAM) is a potential therapeutic target and anchoring molecule for circulating and disseminated tumour cells (CTC/DTC) in liquid biopsy. In this study, we aimed to construct EpCAM-specific immuno-positron emission tomography (immunoPET) imaging probes and assess the diagnostic abilities in preclinical cancer models. METHODS: By engineering six single-domain antibodies (e.g., EPCD1 - 6) targeting EpCAM of different binding properties and labelling with 68Ga (T1/2 = 1.1 h) and 18F (T1/2 = 110 min), we developed a series of EpCAM-targeted immunoPET imaging probes. The probes' pharmacokinetics and diagnostic accuracies were investigated in cell-derived human colorectal (LS174T) and esophageal cancer (OE19) tumour models. RESULTS: Based on in vitro binding affinities and in vivo pharmacokinetics of the first three tracers ([68Ga]Ga-NOTA-EPCD1, [68Ga]Ga-NOTA-EPCD2, and [68Ga]Ga-NOTA-EPCD3), we selected [68Ga]Ga-NOTA-EPCD3 for tumour imaging which showed an average tumour uptake of 2.06 ± 0.124%ID/g (n = 3) in LS174T cell-derived tumour model. Development and characterisation of [18F]AIF-RESCA-EPCD3 showed comparable tumour uptake of 1.73 ± 0.0471%ID/g (n = 3) in the same tumour model. Further validation of [68Ga]Ga-NOTA-EPCD3 in OE19 cell-derived tumour model showed an average tumour uptake of 4.27 ± 1.16%ID/g and liver uptake of 13.5 ± 1.30%ID/g (n = 3). Near-infrared fluorescence imaging with Cy7-EPCD3 confirmed the in vivo pharmacokinetics and relatively high liver accumulation. We further synthesized another three 18F-labeled nanobody tracers ([18F]AIF-RESCA-EPCD4, [18F]AIF-RESCA-EPCD5, and [18F]AIF-RESCA-EPCD6) and found that [18F]AIF-RESCA-EPCD6 had the best pharmacokinetics with low background. [18F]AIF-RESCA-EPCD6 showed explicit uptake in the subcutaneously inoculated OE19 tumour model with an average uptake of 4.70 ± 0.26%ID/g (n = 3). In comparison, the corresponding tumour uptake (0.17 ± 0.25%ID/g, n = 3) in the EPCD6 blocking group was substantially lower (P < 0.001), indicating the targeting specificity of the tracer. CONCLUSIONS: We developed a series of 68Ga/18F-labeled nanobody tracers targeting human EpCAM. ImmunoPET imaging with [18F]AIF-RESCA-EPCD6 may facilitate better use of EpCAM-targeted therapeutics by noninvasively displaying the target's expression dynamics.

Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.

Heat shock proteins are essential molecular chaperones that play crucial roles in stabilizing protein structures, facilitating the repair or degradation of damaged proteins, and maintaining proteostasis and cellular functions. Extensive research has demonstrated that heat shock proteins are highly expressed in cancers and closely associated with tumorigenesis and progression. The "Hallmarks of Cancer" are the core features of cancer biology that collectively define a series of functional characteristics acquired by cells as they transition from a normal state to a state of tumor growth, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabled replicative immortality, the induction of angiogenesis, and the activation of invasion and metastasis. The pivotal roles of heat shock proteins in modulating the hallmarks of cancer through the activation or inhibition of various signaling pathways has been well documented. Therefore, this review provides an overview of the roles of heat shock proteins in vital biological processes from the perspective of the hallmarks of cancer and summarizes the small-molecule inhibitors that target heat shock proteins to regulate various cancer hallmarks. Moreover, we further discuss combination therapy strategies involving heat shock proteins and promising dual-target inhibitors to highlight the potential of targeting heat shock proteins for cancer treatment. In summary, this review highlights how targeting heat shock proteins could regulate the hallmarks of cancer, which will provide valuable information to better elucidate and understand the roles of heat shock proteins in oncology and the mechanisms of cancer occurrence and development and aid in the development of more efficacious and less toxic novel anticancer agents.

Impact of post-COVID-19 changes in outpatient chronic patients' healthcare-seeking behaviors on medical utilization and health outcomes.

INTRODUCTION: This study comprehensively investigates the changes in healthcare utilization among chronic patients with regular outpatient visits to hospitals after the occurrence of Covid-19. The research examines whether patients altered their originally regular medical attendance frequencies due to the pandemic and explores potential negative impacts on the health conditions of those irregular attendees post-pandemic. METHODS: Data for this study were sourced from a database at a medical center in Taiwan. The subjects were chronic patients with regular hospital outpatient visits before the Covid-19 outbreak. The study tracked medical utilization patterns from 2017 to 2022 for different patient characteristics and outpatient behaviors, employing statistical methods such as Repeated Measures ANOVA and Generalized Estimating Equation to analyze changes in healthcare utilization and health status during the post-pandemic period. RESULTS: The results reveal that, compared to the regular group, chronic patients with irregular outpatient visits during the post-pandemic period exhibited a decrease of 5.85 annual outpatient visits, a reduction of NT$20,290.1 in annual medical expenses, and a significantly higher abnormality rate in average biochemical test results by 0.9%. CONCLUSIONS: The findings contribute to understanding the impact of the Covid-19 pandemic on healthcare utilization and health conditions among outpatient chronic disease populations. In response to the new medical landscape in the post-pandemic era, proactive suggestions are made, including providing telemedicine outpatient services and referral-based medical care to meet the needs of the target population, ensuring a continuous and reassuring healthcare model for chronic patients, and mitigating the operational impacts of public health emergencies on hospitals.

Fueling the fight against cancer: Exploring the impact of branched-chain amino acid catalyzation on cancer and cancer immune microenvironment.

Metabolism of Branched-chain amino acids (BCAAs) is essential for the nutrient necessities in mammals. Catalytic enzymes serve to direct the whole-body BCAAs oxidation which involve in the development of various metabolic disorders. The reprogrammed metabolic elements are also responsible for malignant oncogenic processes, and favor the formation of distinctive immunosuppressive microenvironment surrounding different cancers. The impotent immune surveillance related to BCAAs dysfunction is a novel topic to investigate. Here we focus on the BCAA catalysts that contribute to metabolic changes and dysregulated immune reactions in cancer progression. We summarize the current knowledge of BCAA catalyzation, highlighting the interesting roles of BCAA metabolism in the treatment of cancers.

Effect of fatty acid composition on the volatile compounds of pasteurized milk during low-temperature storage.

The change in milk fat during storage greatly influences its flavor. This study investigates the effect of fatty acid composition on milk flavor by analyzing volatile compounds in pasteurized whole milk (PWM) and pasteurized skim milk (PSM) during storage at 4 °C. 33 types of volatile compounds were detected and the content of ketones was highest, followed by esters and aldehydes. Based on variable importance in projection and relative odor activity value, 2-hexenal dimer, acetic acid ethyl ester dimer, acetic acid ethyl ester, and butanal were identified as the key differential volatile compounds. These compounds were found in higher concentrations in PWM than in PSM, indicating a close relationship with the changes in the fatty acid composition of milk fat. Among 11 fatty acids detected in PWM, the content of saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA) decreased by 0.69 % and 49.1 %, respectively, while the content of monounsaturated fatty acids increased by 46.8 % during 15 days storage, which suggests that the oxidation of SFA and PUFA contributed more to the volatile compound formation. Correlation analysis between fatty acid composition and volatile compounds found that fatty acid C18:2 and C16:0 were strongly associated for 2-hexenal, acetic acid ethyl ester, and butanal. These fatty acids were mainly derived from neutral lipids or phospholipids. These findings provide a new perspective for the formation pathway of milk flavor.