Interaction of Ca2+ and Fe3+ in co-precipitation process induced by Virgibacillus dokdonensis and its application.

Biomineralization has garnered significant attention in the field of wastewater treatment due to its notable cost reduction compared to conventional methods. The reinjection water from oilfields containing an exceedingly high concentration of calcium and ferric ions will pose a major hazard in production. However, the utilization of biomineralization for precipitating these ions has been scarcely investigated due to limited tolerance among halophiles towards such extreme conditions. In this study, free and immobilized halophiles Virgibacillus dokdonensis were used to precipitate these ions and the effects were compared, at the same time, biomineralization mechanisms and mineral characteristics were further explored. The results show that bacterial concentration and carbonic anhydrase activity were higher when additionally adding ferric ion based on calcium ion; the content of protein, polysaccharides, deoxyribonucleic acid and humic substances in the extracellular polymers also increased compared to control. Calcium ions were biomineralized into calcite and vaterite with multiple morphology. Due to iron doping, the crystallinity and thermal stability of calcium carbonate decreased, the content of OC = O, NC = O and CO-PO3 increased, the stable carbon isotope values became much more negative, and ß-sheet in minerals disappeared. Higher calcium concentrations facilitated ferric ion precipitation, while ferric ions hindered calcium precipitation. The immobilized bacteria performed better in ferric ion removal, with a precipitation ratio exceeding 90%. Free bacteria performed better in calcium removal, and the precipitation ratio reached a maximum of 56%. This research maybe provides some reference for the co-removal of calcium and ferric ions from the oilfield wastewater.

Entry of ZSWIM4 to the nucleus is crucial for its inhibition of KIT and BMAL1 in gastrointestinal stromal tumors.

BACKGROUND: Zinc finger SWIM-type containing 4 (ZSWIM4) is a zinc finger protein with its function largely uncharacterized. In this study, we aimed to investigate the role of ZSWIM4 in gastrointestinal stromal tumors (GISTs). RESULTS: We found that ZSWIM4 expression is inhibited by the predominantly mutated protein KIT in GISTs, while conversely, ZSWIM4 inhibits KIT expression and downstream signaling. Consistent with the observation, ZSWIM4 inhibited GIST cell survival and proliferation in vitro. RNA sequencing of GISTs from KITV558A/WT mice and KITV558A/WT/ZSWIM4-/- mice showed that loss of ZSWIM4 expression increases the expression of circadian clock pathway member BMAL1 which contributes to GIST cell survival and proliferation. In addition, we found that KIT signaling increases the distribution of ZSWIM4 in the nucleus of GIST cells, and which is important for its inhibition of KIT and BMAL1. In agreement with the results in vitro, the in vivo studies showed that ZSWIM4 deficiency increases the tumorigenesis of GISTs in KITV558A/WT mice. CONCLUSIONS: Taken together, our results revealed that the entry of ZSWIM4 to the nucleus is important for its inhibition of KIT and BMAL1, ultimately attenuating GIST tumorigenesis. The results provide a novel insight in the understanding of signal transduction in GISTs and lay strong theoretical basis for the advancement of GIST treatment.

Quantitative measurements of dual-energy CT parameters in the diagnosis of osteoporosis - a highly sensitive and specific technique: An observational study.

With the aging of the population in our society, osteoporosis (OP) has become one of the chronic diseases that seriously threaten the physical health of the elderly, leading to a heavy burden on healthcare. In recent years, with the continuous development of dual-energy CT (DECT) technology, quantitative measurements of DECT parameters, which is highly sensitive to OP, provides accurate results, is convenient and cost-effective, and is expected to be widely used in bone density testing. This study was aimed to explore the value of quantitative measurements of DECT parameters in diagnosing OP, in order to better guide clinical judgments and treatment. A total of 187 patients who underwent dual-energy X-ray and DECT examinations at Tianjin hospital between January 2022 and June 2023 were included as participants in this study. The bone mineral density (BMD) values of the lumbar spine (L1-L4) were determined using dual-energy X-ray absorptiometry. Simultaneously, CT scans of the lumbar spine (L1-L4) were conducted to measure the CT values of contrast media (CM), mixed-energy image CT values (regular CT value [rCT]), calcium concentration (CaD), as well as fat fraction (FF). Pearson correlation analysis was used to examine the relationship between the quantitative measurements of L1 to L4 vertebral bodies obtained from DECT and BMD. The values of CM, rCT, and CaD in the OP group were all lower than those in the non-OP group with statistical significance (P < .001). Conversely, the fat fraction parameter value in the OP group was significantly higher in contrast with the non-OP group (P = .004); there was a positive correlation between CM, rCT, CaD, and BMD values (R = 0.579, P < .001; R = 0.604, P < .001; R = 0.563, P < .001); CM, rCT, and CaD had high diagnostic value for OP, as evidenced by AUCs of 0.935 (95% CI: 0.900-0.971), 0.956 (95% CI: 0.925-0.987), and 0.926 (95% CI: 0.858-0.954), respectively, all with P values < .001. Quantitative measurement of DECT parameters showed a high sensitivity as well as a high specificity in the diagnosis of OP. It is also highly feasible and holds significant clinical diagnostic value, making it a suitable candidate for widespread application.

Effect of Medicaid expansion on cancer treatment and survival among Medicaid beneficiaries and the uninsured.

BACKGROUND: The Affordable Care Act expanded Medicaid coverage for people with low income in the United States. Expanded insurance coverage could promote more timely access to cancer treatment, which could improve overall survival (OS), yet the long-term effects of Medicaid expansion (ME) remain unknown. We evaluated whether ME was associated with improved timely treatment initiation (TTI) and 3-year OS among patients with breast, cervical, colon, and lung cancers who were affected by the policy. METHODS: Medicaid-insured or uninsured patients aged 40-64 with stage I-III breast, cervical, colon, or non-small cell lung cancer within the National Cancer Database (NCDB). A difference-in-differences (DID) approach was used to compare changes in TTI (within 60 days) and 3-year OS between patients in ME states versus nonexpansion (NE) states before (2010-2013) and after (2015-2018) ME. Adjusted DID estimates for TTI and 3-year OS were calculated using multivariable linear regression and Cox proportional hazards regression models, respectively. RESULTS: ME was associated with a relative increase in TTI within 60 days for breast (DID = 4.6; p < 0.001), cervical (DID = 5.0 p = 0.013), and colon (DID = 4.0, p = 0.008), but not lung cancer (p = 0.505). In Cox regression analysis, ME was associated with improved 3-year OS for breast (DID hazard ratio [HR] = 0.82, p = 0.009), cervical (DID-HR = 0.81, p = 0.048), and lung (DID-HR = 0.87, p = 0.003). Changes in 3-year OS for colon cancer were not statistically different between ME and NE states (DID-HR, 0.77; p = 0.075). CONCLUSIONS: Findings suggest that expanded insurance coverage can improve treatment and survival outcomes among low income and uninsured patients with cancer. As the debate surrounding ME continues nationwide, our findings serve as valuable insights to inform the development of policies aimed at fostering accessible and affordable healthcare for all.

Associations of ambient air pollution exposure and lifestyle factors with incident dementia in the elderly: A prospective study in the UK Biobank.

OBJECTIVE: Dementia is an important disease burden among the elderly, and its occurrence may be profoundly affected by environmental factors. Evidence of the relationship between air pollution and dementia is emerging, but the extent to which this can be offset by lifestyle factors remains ambiguous. METHODS: This study comprised 155,828 elder adults aged 60 years and above in the UK Biobank who were dementia-free at baseline. Cox proportional hazard models were conducted to examine the associations of annual average levels of air pollutants in 2010, including nitrogen dioxide (NO2), nitrogen oxides (NOX), particulate matter (PM2.5, PM10, and PMcoarse) and lifestyle factors recorded at baseline [physical activity (PA), sleep patterns, or smoking status] with incident risk of dementia, and their interactions on both multiplicative and additive scales. RESULTS: During a 12-year period of follow-up, 4,389 incidents of all-cause dementia were identified. For each standarddeviationincrease in ambient NO2, NOX or PM2.5, all-cause dementia risk increases by 1.07-fold [hazard ratio (HR) and 95 % confidence interval (CI) = 1.07 (1.04, 1.10)], 1.05-fold (95 % CI: 1.02, 1.08) and 1.07-fold (95 % CI: 1.04, 1.10), whereas low levels of PA, poor sleep patterns, and smoking are associated with an elevated risk of dementia [HR (95 % CI) = 1.17 (1.09, 1.26), 1.13 (1.00, 1.27), and 1.14 (1.07, 1.21), respectively]. Furthermore, these air pollutants show joint effects with low PA, poor sleep patterns, and smoking on the onset of dementia. The moderate to high levels of PA could significantly or marginally significantly modify the associations between NO2, NOX or PM2.5 (P-int = 0.067, 0.036, and 0.067, respectively) and Alzheimer's disease (AD), but no significant modification effects are found for sleep patterns or smoking status. CONCLUSION: The increased exposures of NO2, NOX, or PM2.5 are associated with elevated risk of dementia among elderly UK Biobank population. These air pollutants take joint effects with low PA, poor sleep patterns, and smoking on the development of dementia. In addition, moderate to high levels of PA could attenuate the incident risk of AD caused by air pollution. Further prospective researches among other cohort populations are warranted to validate these findings.

Mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

An earlier study found that respiratory cadmium chloride (CdCl2) exposure caused COPD-like lung injury. This study aimed to explore whether mitochondrial dysfunction-mediated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury. Adult C57BL/6 mice were exposed to CdCl2 (10 mg/L) aerosol for six months. Beta-galactosidase-positive cells, p21 and p16 were increased in CdCl2-exposed mouse lungs. The in vitro experiments showed that γ-H2AX was elevated in CdCl2-exposed alveolar epithelial cells. The cGAS-STING pathway was activated in CdCl2-exposed alveolar epithelial cells and mouse lungs. Cxcl1, Cxcl9, Il-10, Il-1ß and Mmp2, several senescence-associated secretory phenotypes (SASP), were upregulated in CdCl2-exposed alveolar epithelial cells. Mechanistically, CdCl2 exposure caused SIRT3 reduction and mitochondrial dysfunction in mouse lungs and alveolar epithelial cells. The in vitro experiment found that Sirt3 overexpression attenuated CdCl2-induced alveolar epithelial senescence and SASP. The in vivo experiments showed that Sirt3 gene knockout exacerbated CdCl2-induced alveolar epithelial senescence, alveolar structure damage, airway inflammation and pulmonary function decline. NMN, an NAD+ precursor, attenuated CdCl2-induced alveolar epithelial senescence and SASP in mouse lungs. Moreover, NMN supplementation prevented CdCl2-induced COPD-like alveolar structure damage, epithelial-mesenchymal transition and pulmonary function decline. These results suggest that mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

MRI study on the influence of lumbosacral vertebral body and disc factors on lumbar lordosis in children.

PURPOSE: To evaluate the influence of vertebral and disc wedging on the contribution of lumbar lordosis and the change of disc thickness before and after walking based on MRI. METHODS: Cross-sectional study. A total of 96 normally developing children, aged 5.7 ± 3.0 years old, 55 boys and 41 girls. They were divided into 3 groups: Pre-walking group, Walking group, and Post-walking group. PARAMETERS: lumbar lordosis Angle (LLA), the sum of the lumbar disc wedge Angle (∑D), the sum of the lumbar vertebral body wedge Angle (∑B), disc height (DH). RESULTS: (1) LLA, ∑D, ∑B, and DHL1-S1 were 33.2 ± 8.7°, 14.1 ± 8.6°, 11.9 ± 8.6°, and 6.9 ± 1.2 mm, 7.6 ± 1.4 mm, 8.2 ± 1.6 mm, 8.9 ± 1.7 mm, 8.5 ± 1.8 mm. (2) The difference in LLA values between the Pre-walking and the Post-walking group was statistically significant. DH were significantly different among the three groups. (3) In the Post-walking group, LLA value of girls was significantly higher than that of boys, and DHL3 - 4 and DHL4 - 5 values of girls were significantly lower than that of boys. (4) Age had a low positive correlation with LLA and ∑D and a moderate to strong positive correlation with DH; LLA showed a moderate positive correlation with ∑D, and a low positive correlation with ∑B and DH. CONCLUSION: Age and walking activity are the influencing factors of lumbar lordosis and disc thickening. Walking activity can significantly increase lumbar lordosis, and age is the main factor promoting lumbar disc thickening. DHL4-5 was the thickest lumbar intervertebral disc with the fastest intergroup thickening. Disc wedging contributes more to lumbar lordosis than vertebral wedging.

Inhibition of Indoleamine 2,3-Dioxygenase Exerts Antidepressant-like Effects through Distinct Pathways in Prelimbic and Infralimbic Cortices in Rats under Intracerebroventricular Injection with Streptozotocin.

The application of intracerebroventricular injection of streptozotocin (ICV-STZ) is considered a useful animal model to mimic the onset and progression of sporadic Alzheimer's disease (sAD). In rodents, on day 7 of the experiment, the animals exhibit depression-like behaviors. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme catalyzing the conversion of tryptophan (Trp) to kynurenine (Kyn), is closely related to depression and AD. The present study aimed to investigate the pathophysiological mechanisms of preliminary depression-like behaviors in ICV-STZ rats in two distinct cerebral regions of the medial prefrontal cortex, the prelimbic cortex (PrL) and infralimbic cortex (IL), both presumably involved in AD progression in this model, with a focus on IDO-related Kyn pathways. The results showed an increased Kyn/Trp ratio in both the PrL and IL of ICV-STZ rats, but, intriguingly, abnormalities in downstream metabolic pathways were different, being associated with distinct biological effects. In the PrL, the neuroprotective branch of the Kyn pathway was attenuated, as evidenced by a decrease in the kynurenic acid (KA) level and Kyn aminotransferase II (KAT II) expression, accompanied by astrocyte alterations, such as the decrease in glial fibrillary acidic protein (GFAP)-positive cells and increase in morphological damage. In the IL, the neurotoxicogenic branch of the Kyn pathway was enhanced, as evidenced by an increase in the 3-hydroxy-kynurenine (3-HK) level and kynurenine 3-monooxygenase (KMO) expression paralleled by the overactivation of microglia, reflected by an increase in ionized calcium-binding adaptor molecule 1 (Iba1)-positive cells and cytokines with morphological alterations. Synaptic plasticity was attenuated in both subregions. Additionally, microinjection of the selective IDO inhibitor 1-Methyl-DL-tryptophan (1-MT) in the PrL or IL alleviated depression-like behaviors by reversing these different abnormalities in the PrL and IL. These results suggest that the antidepressant-like effects linked to Trp metabolism changes induced by 1-MT in the PrL and IL occur through different pathways, specifically by enhancing the neuroprotective branch in the PrL and attenuating the neurotoxicogenic branch in the IL, involving distinct glial cells.

Research progress on the effect of sperm chromatin integrity on function and its detection methods.

Sperm chromatin not only carries genetic information such as paternal DNA, but also carries structural proteins, epigenetic information, and higher-order chromatin structures (such as matrix attachment regions and telomeres), etc. These information play an important role in embryonic development. This article mainly reviews the effects of these different information carried by sperm chromatin on sperm function and embryonic development and the research progress of related detection methods, in order to provide a theoretical basis and scientific diagnosis and treatment strategies for the etiology screening of clinical infertility, embryo arrest and recurrent miscarriage, so as to improve the pregnancy outcomes of natural conception and assisted reproduction. Keywords: sperm chromatin; epigenetics; sperm DNA damage; sperm function; higher-order chromatin structures.

Ubiquitin-specific protease 1 facilitates hepatocellular carcinoma progression by modulating mitochondrial fission and metabolic reprogramming via cyclin-dependent kinase 5 stabilization.

Although deubiquitinases (DUBs) have been well described in liver tumorigenesis, their potential roles and mechanisms have not been fully understood. In this study, we identified ubiquitin-specific protease 1 (USP1) as an oncogene with essential roles during hepatocellular carcinoma (HCC) progression. USP1, with elevated expression levels and clinical significance, was identified as a hub DUB for HCC in multiple bioinformatics datasets. Functionally, USP1 overexpression significantly enhanced the malignant behaviors in HCC cell lines and spheroids in vitro, as well as the zebrafish model and the xenograft model in vivo. In contrast, genetic ablation or pharmacological inhibition of USP1 dramatically impaired the phenotypes of HCC cells. Specifically, ectopic USP1 enhanced aggressive properties and metabolic reprogramming of HCC cells by modulating mitochondrial dynamics. Mechanistically, USP1 induced mitochondrial fission by enhancing phosphorylation of Drp1 at Ser616 via deubiquitination and stabilization of cyclin-dependent kinase 5 (CDK5), which could be degraded by the E3 ligase NEDD4L. The USP1/CDK5 modulatory axis was activated in HCC tissues, which was correlated with poor prognosis of HCC patients. Furthermore, Prasugrel was identified as a candidate USP1 inhibitor for targeting the phenotypes of HCC by an extensive computational study combined with experimental validations. Taken together, USP1 induced malignant phenotypes and metabolic reprogramming by modulating mitochondrial dynamics in a CDK5-mediated Drp1 phosphorylation manner, thereby deteriorating HCC progression.

Patient-reported outcomes for the phase 3 FURLONG study of furmonertinib versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer.

Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO). Methods: In this multicentre, double-blind, double-dummy, randomised phase 3 study, patients were 1:1 randomly assigned to receive furmonertinib 80 mg once daily or gefitinib 250 mg once daily. PROs assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Quality-of-Life Questionnaire Lung Cancer 13 were analysed using a mixed model for repeated measures and time-to-event analyses. A difference in score of 10 points or more was deemed clinically relevant. Findings: Three hundred and fifty-seven patients (furmonertinib group, n = 178; gefitinib group, n = 179) received at least one dose of the study drug, all of whom completed at least one PRO assessment. Statistically significant difference of overall score changes from baseline favoured furmonertinib in physical functioning (between-group difference 2.14 [95% CI 0.25-4.04], p = 0.027), nausea/vomiting (-1.56 [95% CI -2.62 to -0.49], p = 0.004), appetite loss (-2.24 [95% CI -4.26 to -0.23], p = 0.029), diarrhoea (-3.36 [95% CI -5.19 to -1.54], p < 0.001), alopecia (-2.62 [95% CI -4.54 to -0.71], p = 0.007), and pain in other parts (-4.55 [95% CI -7.37 to -1.74], p = 0.002), but not reached clinical relevance. Time to deterioration in physical functioning (hazard ratio 0.63 [95% CI 0.42-0.94], p = 0.021), cognitive functioning (0.73 [95% CI 0.54-0.98], p = 0.034), nausea/vomiting (0.64 [95% CI 0.41-0.99], p = 0.042), appetite loss (0.63 [95% CI 0.43-0.92], p = 0.016), diarrhoea (0.63 [95% CI 0.46-0.85], p = 0.002), dyspnoea (0.72 [95% CI 0.53-0.98], p = 0.034), cough (0.67 [95% CI 0.44-1.00], p = 0.049), dysphagia (0.54 [95% CI 0.35-0.83], p = 0.004), and alopecia (0.62 [95% CI 0.42-0.90], p = 0.012) was longer with furmonertinib versus gefitinib. Interpretation: In patients with locally advanced or metastatic EGFR mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib. Funding: Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Standby extracorporeal membrane oxygenation: a better strategy for high-risk percutaneous coronary intervention.

Background: The incidence of cardiac arrest (CA) during percutaneous coronary intervention (PCI) is relatively rare. However, when it does occur, the mortality rate is extremely high. Extracorporeal cardiopulmonary resuscitation (ECPR) has shown promising survival rates for in-hospital cardiac arrests (IHCA), with low-flow time being an independent prognostic factor for CA. However, there is no definitive answer on how to reduce low-flow time. Methods: This retrospective study, conducted at a single center, included 39 patients who underwent ECPR during PCI between January 2016 and December 2022. The patients were divided into two cohorts based on whether standby extracorporeal membrane oxygenation (ECMO) was utilized during PCI: standby ECPR (SBE) (n = 13) and extemporaneous ECPR (EE) (n = 26). We compared the 30-day mortality rates between these two cohorts and investigated factors associated with survival. Results: Compared to the EE cohort, the SBE cohort showed significantly lower low-flow time (P < 0.01), ECMO operation time (P < 0.01), and a lower incidence of acute kidney injury (AKI) (P = 0.017), as well as peak lactate (P < 0.01). Stand-by ECMO was associated with improved 30-day survival (p = 0.036), while prolonged low-flow time (p = 0.004) and a higher SYNTAX II score (p = 0.062) predicted death at 30 days. Conclusions: Standby ECMO can provide significant benefits for patients who undergo ECPR for CA during PCI. It is a viable option for high-risk PCI cases and may enhance the overall prognosis. The low-flow time remains a critical determinant of survival.

Peripherally Restricted CB1 Receptor Inverse Agonist JD5037 Treatment Exacerbates Liver Injury in MDR2-Deficient Mice.

Previous research highlighted the involvement of the cannabinoid CB1 receptor in regulating the physiology of hepatocytes and hepatic stellate cells. The inhibition of the CB1 receptor via peripherally restricted CB1 receptor inverse agonist JD5037 has shown promise in inhibiting liver fibrosis in mice treated with CCl4. However, its efficacy in phospholipid transporter-deficiency-induced liver fibrosis remains uncertain. In this study, we investigated the effectiveness of JD5037 in Mdr2-/- mice. Mdr2 (Abcb4) is a mouse ortholog of the human MDR3 (ABCB4) gene encoding for the canalicular phospholipid transporter. Genetic disruption of the Mdr2 gene in mice causes a complete absence of phosphatidylcholine from bile, leading to liver injury and fibrosis. Mdr2-/- mice develop spontaneous fibrosis during growth. JD5037 was orally administered to the mice for four weeks starting at eight weeks of age. Liver fibrosis, bile acid levels, inflammation, and injury were assessed. Additionally, JD5037 was administered to three-week-old mice to evaluate its preventive effects on fibrosis development. Our findings corroborate previous observations regarding global CB1 receptor inverse agonists. Four weeks of JD5037 treatment in eight-week-old Mdr2-/- mice with established fibrosis led to reduced body weight gains. However, contrary to expectations, JD5037 significantly exacerbated liver injury, evidenced by elevated serum ALT and ALP levels and exacerbated liver histology. Notably, JD5037-treated Mdr2-/- mice exhibited significantly heightened serum bile acid levels. Furthermore, JD5037 treatment intensified liver fibrosis, increased fibrogenic gene expression, stimulated ductular reaction, and upregulated hepatic proinflammatory cytokines. Importantly, JD5037 failed to prevent liver fibrosis formation in three-week-old Mdr2-/- mice. In summary, our study reveals the exacerbating effect of JD5037 on liver fibrosis in genetically MDR2-deficient mice. These findings underscore the need for caution in the use of peripherally restricted CB1R inverse agonists for liver fibrosis treatment, particularly in cases of dysfunctional hepatic phospholipid transporter.

A Chromosome-Level Genome Assembly and Annotation for the Oecanthus rufescens (Orthoptera: Oecanthidae).

Oecanthus is a genus of cricket known for its distinctive chirping and distributed across major zoogeographical regions worldwide. This study focuses on Oecanthus rufescens, and conducts a comprehensive examination of its genome through genome sequencing technologies and bioinformatic analysis. A high-quality chromosome-level genome of O. rufescens was successfully obtained, revealing significant features of its genome structure. The genome size is 877.9 Mb, comprising ten pseudo-chromosomes and 70 other sequences, with a GC content of 41.38% and an N50 value of 157,110,771 bp, indicating a high level of continuity. BUSCO assessment results demonstrate that the genome's integrity and quality are high (of which 96.8% are single-copy and 1.6% are duplicated). Comprehensive genome annotation was also performed, identifying approximately 310 Mb of repetitive sequences, accounting for 35.3% of the total genome sequence, and discovering 15,481 tRNA genes, 4,082 rRNA genes, and 1,212 other noncoding genes. Furthermore, 15,031 protein-coding genes were identified, with BUSCO assessment results showing that 98.4% (of which 96.3% are single-copy and 1.6% are duplicated) of the genes were annotated.

The Multi-institutional Medullary Thyroid Cancer Collaborative Registry (MTCCoRe): Can a rare tumor registry accurately represent the real-world patient population?

BACKGROUND: Large population-based registries, such as the Surveillance, Epidemiology and End Results (SEER) Registry help in the study of rare tumors, including medullary thyroid cancer (MTC), but lack data to understand the natural history of the disease. The Medullary Thyroid Cancer Collaborative Registry (MTCCoRe) is an exhaustive multi-institutional collection of demographic, clinical, and pathologic data. To determine the extent to which MTCCoRe represents the real-world MTC population, we compared characteristics of patients enrolled in MTCCoRe with patients enrolled in population-based cancer registries. METHODS: Comparison of demographic and clinical characteristics of MTC patients who were enrolled in MTCCoRe, Texas Cancer Registry (TCR), California Cancer Registry (CCR), and SEER between 1995-2018. RESULTS: 1,416 patients were identified in MTCCoRe, 329 in TCR, 2,105 in CCR, and 3,820 in SEER. Percentages of patients 20-54 years in MTCCoRe were 58.0%, 50.2% in TCR, 47.2% in CCR, and 44.8% in SEER (p < 0.0001). About half of the patients were female (55.9% in MTCCoRe, 61.4% in TCR, 59% in CCR, and 57.5% in SEER (p=0.3). Percentages of Hispanic and Black patients differed among cohorts (10.1% and 3.8% for MTCCoRe, 23.7% and 8.2% for TCR, 24.8% and 4.9% in CCR, and 15.9% and 8.2% for SEER, respectively; p<0.001). MTCCoRe patients presented with more advanced T and N classifications than patients in the other registries (MTCCoRe, 28.6% T3-4 and 49.4% N1; TCR, 12.7% and 32.2%; CCR, 18.6% and 32.4%; and SEER, 24% and 37.8%; p < 0.0001). Prevalence of M1 disease was 10% in MTCCoRe, 11.9% in TCR, 14.1% in CCR, and 9.5% in SEER (p < 0.0001). In the MTCCoRe, 11.4% underwent systemic therapy (compared to 0.3% in TCR, 5.6% in CCR). CONCLUSIONS: The clinico-demographic profile of patients with MTC enrolled in a multi-institutional registry differs from those enrolled in population-based databases, with lower proportions of Hispanic and Black patients but additive data on treatment modalities. Moving forward, MTCCoRe and other registry and clinical trial enrollment efforts should intentionally include underrepresented groups via community engagement techniques, patient stakeholder involvement, and inclusion of languages other than English in study materials to yield more generalizable results and conclusions.

Chemical fuel-driven transient 2D supramolecular organic frameworks (SOFs): catalysis for green synthesis.

Mimicking the dissipative assemblies found in living systems fueled by bioenergy, we present a novel chemical fuel-driven transient 2D SOF, formed via the redox reaction-driven transient self-assembly of tetraphenylene-based structural units and cucurbit[8]uril (CB[8]). The system was initiated by adding sodium dithionite (SDT) as the fuel, leading to the formation of 2D SOFs through 2 : 1 host-guest complexation between the viologen cation radical and CB[8]. These 2D SOFs then spontaneously disassemble over time as the radicals are oxidized by air. The temporal assembly and lifetimes of these transient SOFs can be controlled by adjusting the concentrations of the fuel. Moreover, the resulting transient 2D SOFs exhibited remarkable potential as catalysts for the green synthesis of benzyl sulfones in water.

Regulating the Distribution and Accumulation of Charged Molecules by Progressive Electroporation for Improved Intracellular Delivery.

The cell membrane separates the intracellular compartment from the extracellular environment, constraining exogenous molecules to enter the cell. Conventional electroporation typically employs high-voltage and short-duration pulses to facilitate the transmembrane transport of molecules impermeable to the membrane under natural conditions by creating temporary hydrophilic pores on the membrane. Electroporation not only enables the entry of exogenous molecules but also directs the intracellular distribution of the electric field. Recent advancements have markedly enhanced the efficiency of intracellular molecule delivery, achieved through the utilization of microstructures, microelectrodes, and surface modifications. However, little attention is paid to regulating the motion of molecules during and after passing through the membrane to improve delivery efficiency, resulting in an unsatisfactory delivery efficiency and high dose demand. Here, we proposed the strategy of regulating the motion of charged molecules during the delivery process by progressive electroporation (PEP), utilizing modulated electric fields. Efficient delivery of charged molecules with an expanded distribution and increased accumulation by PEP was demonstrated through numerical simulations and experimental results. The dose demand can be reduced by 10-40% depending on the size and charge of the molecules. We confirmed the safety of PEP for intracellular delivery in both short and long terms through cytotoxicity assays and transcriptome analysis. Overall, this work not only reveals the mechanism and effectiveness of PEP-enhanced intracellular delivery of charged molecules but also suggests the potential integration of field manipulation of molecular motion with surface modification techniques for biomedical applications such as cell engineering and sensitive cellular monitoring.

[Differences in Soil Fertility and Bacterial Community Structure Between Carbon Inputs such as Biochar and Organic Fertilizer and Their Relationship].

The potato planting area of Guizhou Province ranks second in China. However, due to factors such as climatic conditions and unbalanced fertilization, soil organic matter in potato fields is consumed rapidly and has a large deficit, which affects soil biological function and soil fertility. Biochar and organic fertilizer are effective ways to supplement foreign aid organic matter to improve soil quality. However, the differences in soil fertility and microbial community structure and their relationships under the conditions of organic fertilizer or biochar combined with chemical fertilizer are not clear. In this study, three treatments of conventional fertilization （NPK）, increased application of biochar （NPKB）, and increased application of organic fertilizer （NPKO） were set up to investigate the characteristics of potato rhizosphere soil, bacterial community composition, and diversity； to analyze the effects of these factors on the soil integrated fertility index； and to explore the direct and indirect effects of IFI on soil fertility and bacterial community structure differences between treatments and their driving factors. The results showed that soil pH, available phosphorus （AP）, available potassium （AK）, total nitrogen （TN）, organic carbon （SOC）, and C/N ratio were significantly higher in the NPKB and NPKO treatments than in the NPK treatment （P<0.05）. Soil IFI was greatest for NPKO, followed by NPKB and least for the NPK treatment. A total of 8 214 ASVs were obtained from all the soil samples, belonging to 26 phyla, 75 classes, 165 orders, 176 families, and 251 genera （excluding unidentified fungi）. Proteobacteria, Actinobacteria, and Chloroflexi were the dominant phyla, accounting for 54.85% of all ASVs. Compared to that in the NPK and NPKB treatments, the NPKO treatment had the highest bacterial diversity and number of significantly different taxa, and soil AN, AP, AK, SOC, TN, and IFI were significant correlates of bacterial diversity index （P<0.05）. Additionally, pH, TN, and SOC were significant influencers of bacterial taxa differences （P<0.05）, with importance ranked as TN （70.59%） > SOC （49.42%） > pH （27.08%）. Structural equations suggested that pH-related soil properties and bacterial community diversity were the direct pathways influencing IFI, and soil pH-related soil characteristics could also indirectly affect IFI by affecting bacterial Shannon diversity. These results indicate that soil fertility and bacterial community structure were significantly different and correlated between the biochar and organic fertilizer addition treatments and that pH and bacterial community diversity were the key factors influencing IFI, with the NPKO treatment in particular having the best effect on improving IFI. Considering the effect of soil fertilization and the functional group of bacteria, NPKO is the recommended combination for the best synergistic effect of soil fertilization, that is, N 150 kg·hm-2+P2O5 135 kg·hm-2+K2O 135 kg·hm-2+organic fertilizer 6.6 t·hm-2.

Validation of Acuros for total body irradiation at extended distance.

PURPOSE: Standardized and accurately reported doses are essential in conventional total body irradiation (TBI), especially lung doses. This study evaluates the accuracy of the Acuros algorithm in predicting doses for extended-distance TBI. METHODS: Measurements and calculations were done with both 6 and 18 MV. Tissue Maximum Ratio (TMR), output and off axis ratios (OAR) were measured at 200 and 500 cm source to detector distance and compared to Acuros calculated values. Two end-to-end tests were carried out, one with an in-house phantom (solid water and Styrofoam) with inserted ion chambers and the other was with the Imaging and Radiation Oncology Core (IROC) TBI anthropomorphic phantom equipped with TLDs. The end-to-end test was done for 6 and 18 MV both with and without lung blocks. The source to midplane distance for both phantoms were at 518 and 508 cm respectively. Lung blocks were placed at the phantom surface and a beam spoiler was positioned 30 cm from the surface of the phantoms as per our clinical set up. RESULTS: The agreement between measured and calculated TMR, output and off axis ratios for both 6 and 18 MV were within 2%. Ion chamber measurements in both the Styrofoam and solid water for both energies carried out with and without lung blocks were within 2% of calculated values. TLD measured doses for both 6 and 18 MV in the IROC phantom were within 5% of calculated doses which is within the uncertainty of the TLD measurement. CONCLUSIONS: The results indicate that the clinical beam model for Acuros 16.1 commissioned at standard clinical distances is capable of calculating doses accurately at extended distances up to 500 cm.

Analysis of Phenotypes Associated with Deficiency of PAX6 Haplotypes in Chinese Aniridia Families.

OBJECTIVE: To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency. METHODS: A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives. The clinical feature analysis included the evaluation of visual acuity, intraocular pressure, slit-lamp anterior segment examination, fundus photography, and spectral domain optical coherence tomography. To identify the mutation responsible for aniridia, targeted next-generation sequencing was used as a beneficial technique. RESULTS: A total of 4 mutations were identified, consisting of two novel frameshift mutations (c.314delA, p.K105Sfs*33 and c.838_845dup AACACACC, p.S283Tfs*85), along with two recurring nonsense mutations (c.307C>T, p.R103X and c.619A>T, p.K207*). Complete iris absence, macular foveal hypoplasia, and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families, while corneal lesions, cataracts, and glaucoma exhibited heterogeneity both among the families and within the same family. CONCLUSION: In our study, two novel PAX6 mutations associated with aniridia were identified in Chinese families, which expanded the phenotypic and genotypic spectrum of PAX6 mutations. We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.