Excessive load promotes temporomandibular joint chondrocyte apoptosis via Piezo1/endoplasmic reticulum stress pathway.

Excessive load on the temporomandibular joint (TMJ) is a significant factor in the development of TMJ osteoarthritis, contributing to cartilage degeneration. The specific mechanism through which excessive load induces TMJ osteoarthritis is not fully understood; however, mechanically-activated (MA) ion channels play a crucial role. Among these channels, Piezo1 has been identified as a mediator of chondrocyte catabolic responses and is markedly increased in osteoarthritis. Our observations indicate that, under excessive load conditions, endoplasmic reticulum stress in chondrocytes results in apoptosis of the TMJ chondrocytes. Importantly, using the Piezo1 inhibitor GsMTx4 demonstrates its potential to alleviate this condition. Furthermore, Piezo1 mediates endoplasmic reticulum stress in chondrocytes by inducing calcium ion influx. Our research substantiates the role of Piezo1 as a pivotal ion channel in mediating chondrocyte overload. It elucidates the link between excessive load, cell apoptosis, and calcium ion influx through Piezo1. The findings underscore Piezo1 as a key player in the pathogenesis of TMJ osteoarthritis, shedding light on potential therapeutic interventions for this condition.

Excess burden of respiratory and abdominal conditions following COVID-19 infections during the ancestral and Delta variant periods in the United States: An EHR-based cohort study from the RECOVER program.

IMPORTANCE: The frequency and characteristics of post-acute sequelae of SARS-CoV-2 infection (PASC) may vary by SARS-CoV-2 variant. OBJECTIVE: To characterize PASC-related conditions among individuals likely infected by the ancestral strain in 2020 and individuals likely infected by the Delta variant in 2021. DESIGN: Retrospective cohort study of electronic medical record data for approximately 27 million patients from March 1, 2020-November 30, 2021. SETTING: Healthcare facilities in New York and Florida. PARTICIPANTS: Patients who were at least 20 years old and had diagnosis codes that included at least one SARS-CoV-2 viral test during the study period. EXPOSURE: Laboratory-confirmed COVID-19 infection, classified by the most common variant prevalent in those regions at the time. MAIN OUTCOME(S) AND MEASURE(S): Relative risk (estimated by adjusted hazard ratio [aHR]) and absolute risk difference (estimated by adjusted excess burden) of new conditions, defined as new documentation of symptoms or diagnoses, in persons between 31-180 days after a positive COVID-19 test compared to persons without a COVID-19 test or diagnosis during the 31-180 days after the last negative test. RESULTS: We analyzed data from 560,752 patients. The median age was 57 years; 60.3% were female, 20.0% non-Hispanic Black, and 19.6% Hispanic. During the study period, 57,616 patients had a positive SARS-CoV-2 test; 503,136 did not. For infections during the ancestral strain period, pulmonary fibrosis, edema (excess fluid), and inflammation had the largest aHR, comparing those with a positive test to those without a COVID-19 test or diagnosis (aHR 2.32 [95% CI 2.09 2.57]), and dyspnea (shortness of breath) carried the largest excess burden (47.6 more cases per 1,000 persons). For infections during the Delta period, pulmonary embolism had the largest aHR comparing those with a positive test to a negative test (aHR 2.18 [95% CI 1.57, 3.01]), and abdominal pain carried the largest excess burden (85.3 more cases per 1,000 persons). CONCLUSIONS AND RELEVANCE: We documented a substantial relative risk of pulmonary embolism and a large absolute risk difference of abdomen-related symptoms after SARS-CoV-2 infection during the Delta variant period. As new SARS-CoV-2 variants emerge, researchers and clinicians should monitor patients for changing symptoms and conditions that develop after infection.

Evaluating and Enhancing Large Language Models' Performance in Domain-specific Medicine: Explainable LLM with DocOA.

BACKGROUND: Evaluating and Enhancing Large Language Models' Performance in Domain-specific Medicine: Explainable LLM with DocOA. OBJECTIVE: This study focused on evaluating and enhancing the clinical capabilities and explainability of LLMs in specific domains, using osteoarthritis (OA) management as a case study. METHODS: A domain specific benchmark framework was developed, which evaluate LLMs across a spectrum from domain-specific knowledge to clinical applications in real-world clinical scenarios. DocOA, a specialized LLM designed for OA management integrating retrieval-augmented generation (RAG) and instructional prompts, was developed. It can identify the clinical evidence upon which its answers are based through RAG, thereby demonstrating the explainability of those answers. The study compared the performance of GPT-3.5, GPT-4, and a specialized assistant, DocOA, using objective and human evaluations. RESULTS: Results showed that general LLMs like GPT-3.5 and GPT-4 were less effective in the specialized domain of OA management, particularly in providing personalized treatment recommendations. However, DocOA showed significant improvements. CONCLUSIONS: This study introduces a novel benchmark framework which assesses the domain-specific abilities of LLMs in multiple aspects, highlights the limitations of generalized LLMs in clinical contexts, and demonstrates the potential of tailored approaches for developing domain-specific medical LLMs.

Response-adapted ultra-low-dose 4 Gy radiation as definitive therapy of gastric MALT lymphoma: a single-centre, pilot trial.

BACKGROUND: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach. METHODS: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment. FINDINGS: Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths. INTERPRETATION: Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity. FUNDING: National Cancer Institute.

Weighted gene co-expression network analysis reveals genes related to growth performance in Hu sheep.

Hu sheep are a unique breed in our country with great reproductive potential, the extent of whose breeding has been steadily rising in recent years. The study subjects in this experiment were 8-month-old Hu sheep (n = 112). First of all, the growth performance, slaughter performance and meat quality of their eye muscle quality were assessed, meanwhile their live weight, carcass weight, body length, body height, chest circumference, chest depth and tube circumference were respectively 33.81 ± 5.47 kg, 17.43 ± 3.21 kg, 60.36 ± 4.41 cm, 63.25 ± 3.88 cm, 72.03 ± 5.02 cm, 30.70 ± 2.32 cm and 7.36 ± 0.56 cm, with a significant difference between rams and ewes (P < 0.01). Following that, transcriptome sequencing was done, and candidate genes related to growth performance were identified using the weighted co-expression network analysis (WGCNA) approach, which was used to identified 15 modules, with the turquoise and blue modules having the strongest association with growth and slaughter performance, respectively. We discovered hub genes such as ARHGAP31, EPS8, AKT3, EPN1, PACS2, KIF1C, C12H1orf115, FSTL1, PTGFRN and IFIH1 in the gene modules connected with growth and slaughter performance. Our research identifies the hub genes associated with the growth and slaughter performance of Hu sheep, which play an important role in their muscle growth, organ and cartilage development, blood vessel development and energy metabolic pathways. Our findings might lead to the development of potentially-useful biomarkers for the selection of growth and slaughterer performance-related attributes of sheep and other livestock.

Biometric factors associated with the postoperative visual performance of a multifocal intraocular lens.

Purpose: To identify the biometric factors associated with postoperative visual performance after uneventful phacoemulsification with multifocal intraocular lens (MIOL) implantation. Methods: In this retrospective cohort study, 72 eyes of 72 patients implanted with the HumanOptics Diff-aAY MIOL were included. Preoperative examination data including the white-to-white distance (WTW), anterior chamber depth (ACD), axial length and corneal astigmatism were gathered through the electronic medical records. One month postoperatively, the pupil parameters, corneal aberrations, corneal astigmatism, IOL tilts and IOL decentrations were measured using an OPD-Scan III aberrometer. Postoperative visual performance parameters were recorded as the visual acuity, depth of focus, modulation transfer function (MTF) and point spread function (PSF) values, area under log contrast sensitivity function (AULCSF), retinal straylight and visual function questionnaire scores. Univariate and multivariate linear regression analyses were then performed to evaluate the associations between the potential biometric factors and postoperative visual outcomes. Results: Younger age predicted greater MTF and PSF values, better AULCSF and better retinal straylight (P < 0.05). A lower corneal trefoil predicted better MTF and PSF values (P < 0.05). Smaller IOL decentration predicted better distance-corrected near visual acuity, greater AULCSF and better retinal straylight (P < 0.05). A less negative spherical equivalent (SE) predicted better MTF values (P = 0.017), while a more negative SE predicted better Visual Function Index-14 (VF-14) questionnaire scores and satisfaction scores (P < 0.05). A higher IOL power predicted better best corrected distance visual acuity (P = 0.005). Lower preoperative corneal astigmatism predicted greater MTF values (P = 0.020). Lower postoperative corneal astigmatism, smaller corneal high-order aberrations (HOAs), smaller photopic pupil size, larger WTW and deeper ACD predicted a better AULCSF (P < 0.05). Conclusions: IOL decentration, IOL power, age, preoperative and postoperative corneal astigmatism, SE, photopic pupil size, corneal trefoil, WTW, ACD and corneal HOAs were significantly associated with postoperative visual performance. These findings might aid in patient selection prior to MIOL implantation.

Combined Genetic Association and Differed Expression Analysis of UBE2L3 Uncovers a Genetic Regulatory Role of (Immuno)proteasome in IgA Nephropathy.

Introduction: IgA nephropathy (IgAN) is a leading cause of end-stage renal disease. The exact pathogenesis of IgAN is not well defined, but some genetic studies have led to a novel discovery that the (immuno)proteasome probably plays an important role in IgAN. Methods: We firstly analyzed the association of variants in the UBE2L3 region with susceptibility to IgAN in 3,495 patients and 9,101 controls, and then analyzed the association between lead variant and clinical phenotypes in 1,803 patients with regular follow-up data. The blood mRNA levels of members of the ubiquitin-proteasome system including UBE2L3 were analyzed in peripheral blood mononuclear cells from 53 patients and 28 healthy controls. The associations between UBE2L3 and the expression levels of genes involved in Gd-IgA1 production were also explored. Results: The rs131654 showed the most significant association signal in UBE2L3 region (OR: 1.10, 95% CI: 1.04-1.16, p = 2.29 × 10-3), whose genotypes were also associated with the levels of Gd-IgA1 (p = 0.04). The rs131654 was observed to exert cis-eQTL effects on UBE2L3 in various tissues and cell types, particularly in immune cell types in multiple databases. The UBE2L3, LUBAC, and proteasome subunits were highly expressed in patients compared with healthy controls. High expression levels of UBE2L3 were not only associated with higher proteinuria (r = 0.34, p = 0.01) and lower eGFR (r = -0.28, p = 0.04), but also positively correlated with the gene expression of LUBAC and other proteasome subunits. Additionally, mRNA expression levels of UBE2L3 were also positively correlated with IL-6 and RELA, but negatively correlated with the expression levels of the key enzyme in the process of glycosylation including C1GALT1 and C1GALT1C1. Conclusion: In conclusion, by combined genetic association and differed expression analysis of UBE2L3, our data support a role of genetically conferred dysregulation of the (immuno)proteasome in regulating galactose-deficient IgA1 in the development of IgAN.

Application and Development of Electrospun Nanofiber Scaffolds for Bone Tissue Engineering.

Nanofiber scaffolds have gained significant attention in the field of bone tissue engineering. Electrospinning, a straightforward and efficient technique for producing nanofibers, has been extensively researched. When used in bone tissue engineering scaffolds, electrospun nanofibers with suitable surface properties promote new bone tissue growth and enhance cell adhesion. Recent advancements in electrospinning technology have provided innovative approaches for scaffold fabrication in bone tissue engineering. This review comprehensively examines the utilization of electrospun nanofibers in bone tissue engineering scaffolds and evaluates the relevant literature. The review begins by presenting the fundamental principles and methodologies of electrospinning. It then discusses various materials used in the production of electrospun nanofiber scaffolds for bone tissue engineering, including natural and synthetic polymers, as well as certain inorganic materials. The challenges associated with these materials are also described. The review focuses on novel electrospinning techniques for scaffold construction in bone tissue engineering, such as multilayer nanofibers, multifluid electrospinning, and the integration of electrospinning with other methods. Recent advancements in electrospinning technology have enabled the fabrication of precisely aligned nanofiber scaffolds with nanoscale architectures. These innovative methods also facilitate the fabrication of biomimetic structures, wherein bioactive substances can be incorporated and released in a controlled manner for drug delivery purposes. Moreover, they address issues encountered with traditional electrospun nanofibers, such as mechanical characteristics and biocompatibility. Consequently, the development and implementation of novel electrospinning technologies have revolutionized scaffold fabrication for bone tissue engineering.

Synergistic effect of modified anhydrous magnesium carbonate and hexaphenoxycyclotriphosphazene on flame retardancy of ethylene-vinyl acetate copolymer.

Ethylene-vinyl acetate copolymer (EVA) is widely used in various applications; however, its flammability limits its application in wire and cable industries. In this study, 3-methacryloxypropyltrimethoxysilane (KH570) was successfully grafted onto the surface of anhydrous magnesium carbonate (AMC) by alkali activation treatment. The KH570 modified AMC (AMC@KH570) was then introduced into the EVA matrix along with hexaphenoxycyclotriphosphazene (HPCTP) to assess their effects on the flame retardancy and mechanical properties of EVA composites. The results illustrate a significant synergistic effect in enhancing the flame retardancy of EVA composites by using AMC@KH570 and HPCTP, and the limiting oxygen index (LOI) and vertical burning test (UL-94) of EVA filled with 5 wt% HPCTP and 45 wt% AMC@KH570 (mAMC/H-45-5) reached 27.6% and V-0, respectively. The flame retardant mechanism was investigated by thermogravimetric/infrared (TG-IR) spectroscopy and residual carbon composition analysis. The results show that the thermal decomposition of AMC@KH570 and HPCTP consists of gas dilution, free radical quenching, and catalytic carbonization. Furthermore, KH570 works as a bridge to improve the compatibility of AMC and EVA matrix, which offsets the mechanical loss of EVA to some extent. The present research provides a new path to modify AMC and fabricate EVA composites with excellent flame retardant properties.

Temperature effects on plasmalogen profile and quality characteristics in Pacific oyster (Crassostrea gigas) during depuration.

The quality of Pacific oyster (Crassostrea gigas) can be affected by many factors during depuration, in which temperature is the major element. In this study, we aim to determine the quality and plasmalogen changes in C. gigas depurated at different temperatures. The quality was significantly affected by temperature, represented by varying survival rate, glycogen content, total antioxidant capacity, alkaline phosphatase activity between control and stressed groups. Targeted MS analysis demonstrated that plasmalogen profile was significantly changed during depuration with PUFA-containing plasmalogen species being most affected by temperature. Proteomics analysis and gene expression assay further verified that plasmalogen metabolism is regulated by temperature, specifically, the plasmalogen synthesis enzyme EPT1 was significantly downregulated by high temperature and four plasmalogen-related genes (GPDH, PEDS, Pex11, and PLD1) were transcriptionally regulated. The positive correlations between the plasmalogen level and quality characteristics suggested plasmalogen could be regarded as a quality indicator of oysters during depuration.

Prediction model of deep vein thrombosis risk after lower extremity orthopedic surgery.

Purpose: This investigation was conceived to engineer and appraise a pioneering clinical nomogram, crafted to bridge the extant chasm in literature regarding the postoperative risk stratification for deep vein thrombosis (DVT) in the aftermath of lower extremity orthopedic procedures. This novel tool offers a sophisticated and discerning algorithm for risk prediction, heretofore unmet by existing methodologies. Methods: In this retrospective observational study, clinical records of hospitalized patients who underwent lower extremity orthopedic surgery were collected at the Wuxi TCM Hospital Affiliated to the Nanjing University of Chinese Medicine between Jan 2017 and Oct 2019. The univariate and multivariate analysis with the backward stepwise method was applied to select features for the predictive nomogram. The performance of the nomogram was evaluated with respect to its discriminant capability, calibration ability, and clinical utility. Result: A total of 5773 in-hospital patients were eligible for the study, with the incidence of deep vein thrombosis being approximately 1 % in this population. Among 31 variables included, 5 of them were identified to be the predictive features in the nomogram, including age, mean corpuscular hemoglobin concentration (MCHC), D-dimer, platelet distribution width (PDW), and thrombin time (TT). The area under the receiver operating characteristic (ROC) curve in the training and validation cohort was 85.9 % (95%CI: 79.96 %-90.04 %) and 85.7 % (95%CI: 78.96 %-90.69 %), respectively. Both the calibration curves and decision curve analysis demonstrated the overall satisfactory performance of the model. Conclusion: Our groundbreaking nomogram is distinguished by its unparalleled accuracy in discriminative and calibrating functions, complemented by its tangible clinical applicability. This innovative instrument is set to empower clinicians with a robust framework for the accurate forecasting of postoperative DVT, thus facilitating the crafting of bespoke and prompt therapeutic strategies, aligning with the rigorous standards upheld by the most esteemed biomedical journals.

The association between pulse wave velocity and pregnancy-associated diseases: A systematic review and meta-analysis.

Background: Maintaining healthy vascular structure and function is important for a healthy pregnancy. Obesity is a well-known predictor for poor postoperative outcomes of vascular surgery. However, the association between pulse wave velocity (PWV), a well-recognized parameter for arterial stiffness assessment, and pregnancy-associated diseases is still unclear. Therefore, we conducted this systematic review, and a meta-analysis was performed to assess the relevant associations. Methods: We systematically searched the Web of Science and PubMed databases to obtain articles on PWV and pregnancy-associated diseases published before April 2023. The mean with standard deviation was used to assess the differences in PWV in pregnant women with or without relevant diseases. Subgroup analysis was conducted according to specific types of PWV. The Newcastle‒Ottawa Scale was used to evaluate the quality of the enrolled studies. Results: A total of 6488 individuals from 21 studies were included. All enrolled studies were high-quality. Overall, the PWV was elevated in pregnant women who suffered from preeclampsia (mean difference (MD) = 0.67, 95 % confidence interval (CI): 0.51,0.83, P < 0.00001), hypertension (MD = 1.04, 95 % CI: 1.00,1.08, P < 0.00001), gestational diabetes mellitus (MD = 0.34, 95%CI: 0.19,0.48, P < 0.00001), and diabetes (MD = 0.49, 95%CI: 0.27,0.70, P < 0.00001). Subgroup analysis based on specific types of PWV showed similar results. Conclusion: In our study, PWV is elevated in pregnancy-associated diseases, including preeclampsia, hypertension, and diabetes. The PWV assessment should be regarded as a clinical routine for pregnant women to prevent and manage cardiovascular diseases during pregnancy.

Novel biocompatible N-rich AIE fluorescent probe for live cell imaging and visual onsite detection of uranium.

A sensitive and biocompatible N-rich probe for rapid visual uranium detection was constructed by grafting two trianiline groups to 2,6-bis(aminomethyl)pyridine. Possessing excellent aggregation-induced emission (AIE) property and the advantages to form multidentate chelate with U selectively, the probe has been applied successfully to visualize uranium in complex environmental water samples and living cells, demonstrating outstanding anti-interference ability against large equivalent of different ions over a wide effective pH range. A large linear range (1.0 × 10-7-9.0 × 10-7 mol/L) and low detection limit (72.6 nmol/L, 17.28 ppb) were achieved for the visual determination of uranium. The recognition mechanism, photophysical properties, analytical performance and cytotoxicity were systematically investigated, demonstrating high potential for fast risk assessment of uranium pollution in field and in vivo.

Defective Tungsten Oxides with Stacking Faults for Proton Exchange Membrane Green-Hydrogen Generation.

Defects can introduce atomic structural modulation and tailor performance of materials. Herein, it demonstrates that semiconductor WO3 with inert electrocatalytic behavior can be activated through defect-induced tensile strains. Structural characterizations reveal that when simply treated in Ar/H2 atmosphere, oxygen vacancies will generate in WO3 and cause defective structures. Stacking faults are found in defects, thus modulating electronic structure and transforming electrocatalytic-inert WO3 into highly active electrocatalysts. Density functional theory (DFT) calculations are performed to calculate *H adsorption energies on various WOx surfaces, revealing the oxygen vacancy composition and strain predicted to optimize the catalytic activity of hydrogen evolution reaction (HER). Such defective tungsten oxides can be integrated into commercial proton exchange membrane (PEM) electrolyser with comparable performance toward Pt-based PEM. This work demonstrates defective metal oxides as promising non-noble metal catalysts for commercial PEM green-hydrogen generation.

A novel nomogram and prognostic factor for metastatic soft tissue sarcoma survival.

Background: This study represented the inaugural effort to develop predictive survival nomograms for metastatic soft tissue sarcoma (mSTS) patients in the era of immune checkpoint inhibitors. Method: From the Surveillance, Epidemiology, and End Results (SEER) program database, we extracted 3078 eligible patients with mSTS between 2016 and 2022. Kaplan-Meier survival analysis, univariate and multivariable Cox analyses, and univariate and multivariable logistic analyses were conducted. Subsequently, predictive nomograms were constructed. Clinical effectiveness was validated using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA) methods. Results: We used the SEER database to include 3078 eligible patients with mSTS between 2016 and 2022. All the eligible patients were randomly allocated in a ratio of 6:4 and stratified into a training group (n = 1846) and a validation group (n = 1232). In the multivariate Cox analysis, age, race, marital status, pathological grade, histologic subtype, surgery, and chemotherapy were identified as independent prognostic factors. These factors were used to construct the nomogram to predict the 1-, 3-, and 5-year OS of mSTS patients. The C-index for the training cohort and the validation cohort was 0.722(95% confidence interval [CI]: 0.708-0.736), and 0.716(95% CI: 0.698-0.734), respectively. The calibration curves for 1-, 3-, and 5-year OS probability demonstrated excellent calibration between the predicted and the actual survival. The AUC values of the nomogram at 1-, 3-, and 5-year were 0.785, 0.767, and 0.757 in the training cohort, 0.773, 0.754, and 0.751 in the validation cohort, respectively. Furthermore, DCA indicated the favorable clinical utility of the nomogram in both cohorts. The risk stratification system was constructed using the established nomogram, which enhanced prediction accuracy, aided clinicians in identifying high-risk patients and informing treatment decisions. Conclusion: This study marked the inaugural effort in constructing predictive survival nomograms mSTS patients in the era of immune checkpoint inhibitors. The robustly constructed nomograms, alongside actual outcomes, offered valuable insights to inform follow-up management strategies.

Integrative immunophenotypic and genetic characterization of acute myeloid leukemia with CBFB rearrangement.

OBJECTIVES: We sought to characterize the immunophenotype of acute myeloid leukemia (AML) with CBFB rearrangement and correlate the results with cytogenetic and molecular data. METHODS: Sixty-one cases of AML with CBFB rearrangement were evaluated. RESULTS: The sample population consisted of 33 men and 28 women, with a median age of 49 years. Flow cytometry immunophenotypic analysis showed that myeloblasts were positive for CD34 and CD117 in all cases, and myeloperoxidase was positive in 52 of 55 (95%) cases. The most common abnormalities included decreased CD38 in 90%, increased CD13 in 85%, increased CD123 in 84%, and decreased HLA-DR in 84% of cases. Monocytes were increased, with a mature immunophenotype, and accounted for 23.7% of total cells. Among 60 cases with available karyotype, inv(16)(p13.1q22) was most common in 50 (83%) cases, followed by t(16;16) (p13.1;q22) in 6 (10%). Type A CBFB::MYH11 transcript was most common, detected in 84% of cases. Mutational analysis showed mutations of NRAS in 37%, FLT3 in 25%, and KIT in 24% of cases. Comparing cases with type A vs non-type A transcripts, blasts in type A cases more frequently exhibited CD64 positivity and increased CD13 levels while showing a lower frequency of CD7 and CD56 expression. Trisomy 22 and mutations in KIT, NF1, and TET2 were identified only in cases with type A transcript. CONCLUSIONS: Myeloblasts of AML with CBFB rearrangement are positive for CD34, CD117, and myeloperoxidase. These neoplasms most frequently carry inv(16)(p13.1q22) and type A fusion transcript. NRAS mutation was the most common mutation. Some immunophenotypic and genetic correlations occurred with different types of transcripts.

Fluorescent small molecule donors.

Small molecule donors (SMDs) play subtle roles in the signaling mechanism and disease treatments. While many excellent SMDs have been developed, dosage control, targeted delivery, spatiotemporal feedback, as well as the efficiency evaluation of small molecules are still key challenges. Accordingly, fluorescent small molecule donors (FSMDs) have emerged to meet these challenges. FSMDs enable controllable release and non-invasive real-time monitoring, providing significant advantages for drug development and clinical diagnosis. Integration of FSMDs with chemotherapeutic, photodynamic or photothermal properties can take full advantage of each mode to enhance therapeutic efficacy. Given the remarkable properties and the thriving development of FSMDs, we believe a review is needed to summarize the design, triggering strategies and tracking mechanisms of FSMDs. With this review, we compiled FSMDs for most small molecules (nitric oxide, carbon monoxide, hydrogen sulfide, sulfur dioxide, reactive oxygen species and formaldehyde), and discuss recent progress concerning their molecular design, structural classification, mechanisms of generation, triggered release, structure-activity relationships, and the fluorescence response mechanism. Firstly, from the large number of fluorescent small molecular donors available, we have organized the common structures for producing different types of small molecules, providing a general strategy for the development of FSMDs. Secondly, we have classified FSMDs in terms of the respective donor types and fluorophore structures. Thirdly, we discuss the mechanisms and factors associated with the controlled release of small molecules and the regulation of the fluorescence responses, from which universal guidelines for optical properties and structure rearrangement were established, mainly involving light-controlled, enzyme-activated, reactive oxygen species-triggered, biothiol-triggered, single-electron reduction, click chemistry, and other triggering mechanisms. Fourthly, representative applications of FSMDs for trackable release, and evaluation monitoring, as well as for visible in vivo treatment are outlined, to illustrate the potential of FSMDs in drug screening and precision medicine. Finally, we discuss the opportunities and remaining challenges for the development of FSMDs for practical and clinical applications, which we anticipate will stimulate the attention of researchers in the diverse fields of chemistry, pharmacology, chemical biology and clinical chemistry. With this review, we hope to impart new understanding thereby enabling the rapid development of the next generation of FSMDs.

The association between dietary vitamin B1 intake and constipation: a population-based study.

BACKGROUND: Numerous researches have indicated a correlation between the intake of dietary micronutrients and the occurrence of constipation. Nevertheless, the correlation between constipation and vitamin B1 remains uninvestigated. The main aim of this research was to examine the association between chronic constipation and the consumption of vitamin B1 in the diet among adult participants of the National Health and Nutrition Examination Survey (NHANES). METHODS: This study used data from the NHANES, a survey on health and nutrition conducted between 2005 and 2010. The respondents' dietary information was gathered by utilizing the 24-hour dietary records. Various statistical analyses, such as multiple logistic regression, subgroup analysis, and curve-fitting analysis, were employed to investigate the correlation between dietary intake of vitamin B1 and chronic constipation. RESULTS: In the trial, there were 10,371 participants, out of which 1,123 individuals (10.8%) were identified as having chronic constipation. Fully adjusted multiple logistic regression analyses showed that increasing dietary intake of vitamin B1 (OR = 0.87, 95% CI: 0.77-0.99) was significantly associated with a reduced risk of constipation. Following adjustment for multiple variables in Model 3, the odds ratio (OR) and 95% confidence interval (CI) for the third tertile, in comparison to the first tertile (reference group), was 0.80 (0.65, 0.99). In addition, subgroup analyses and interaction tests showed a significant inverse association between vitamin B1 intake and the prevalence of constipation, especially among men, non-hypertensive, and non-diabetic individuals (all P-values less than 0.05). CONCLUSION: This research uncovered an inverse correlation between the consumption of vitamin B1 in the diet and the occurrence of chronic constipation. One potential explanation for this phenomenon is that the consumption of vitamin B1 in one's diet is linked to the softening of stools and an augmented occurrence of colonic peristalsis. Additional extensive prospective research is required to thoroughly examine the significance of thiamine in long-term constipation.

Identification of shared gene signatures in major depressive disorder and triple-negative breast cancer.

BACKGROUND: Patients with major depressive disorder (MDD) have an increased risk of breast cancer (BC), implying that these two diseases share similar pathological mechanisms. This study aimed to identify the key pathogenic genes that lead to the occurrence of both triple-negative breast cancer (TNBC) and MDD. METHODS: Public datasets GSE65194 and GSE98793 were analyzed to identify differentially expressed genes (DEGs) shared by both datasets. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape to identify key PPI genes using cytoHubba. Hub DEGs were obtained from the intersection of hub genes from a PPI network with genes in the disease associated modules of the Weighed Gene Co-expression Network Analysis (WGCNA). Independent datasets (TCGA and GSE76826) and RT-qPCR validated hub gene expression. RESULTS: A total of 113 overlapping DEGs were identified between TNBC and MDD. The PPI network was constructed, and 35 hub DEGs were identified. Through WGCNA, the blue, brown, and turquoise modules were recognized as highly correlated with TNBC, while the brown, turquoise, and yellow modules were similarly correlated with MDD. Notably, G3BP1, MAF, NCEH1, and TMEM45A emerged as hub DEGs as they appeared both in modules and PPI hub DEGs. Within the GSE65194 and GSE98793 datasets, G3BP1 and MAF exhibited a significant downregulation in TNBC and MDD groups compared to the control, whereas NCEH1 and TMEM45A demonstrated a significant upregulation. These findings were further substantiated by TCGA and GSE76826, as well as through RT-qPCR validation. CONCLUSIONS: This study identified G3BP1, MAF, NCEH1 and TMEM45A as key pathological genes in both TNBC and MDD.