Metformin Attenuates Vocal Fold Fibrosis via AMPK Signaling.

Vocal fold fibrosis is a challenging condition with no clear consensus on effective treatment methods. Given the demonstrated efficacy of metformin in treating various fibrotic diseases, we hypothesized that metformin could reduce vocal fold fibrosis via the AMPK signaling pathway. In our study, we induced vocal fold injury in rabbits and administered metformin intraperitoneally at a dose of 250 mg/kg two weeks post-injury. Four weeks after the injury, vocal folds were excised and analyzed for fibrosis using Masson's trichrome staining, immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR), and Western blotting. In vitro, vocal fold fibroblasts treated with metformin (10 µM) ± TGF-ß1 (10 ng/mL) were utilized to assess metformin's antifibrotic effects, with Compound C (10 µM) employed to inhibit AMPK signaling. Our results demonstrate that metformin significantly improved the structural integrity of the vocal fold lamina, reduced collagen deposition, and decreased the expression levels of COL1A1 and α-SMA. Furthermore, metformin activated the AMPK signaling pathway in vocal fold fibroblasts, resulting in decreased expression of COL1A1, α-SMA, TGF-ß, Smad2, and Smad3. These findings suggest that metformin attenuates vocal fold fibrosis by modulating the AMPK signaling pathway, providing a foundation for developing new therapeutic options for vocal fold fibrosis.

Quantitative physics-physiology relationship modeling of human emotional response to Shu music.

Music perception is one of the most complex human neurophysiological phenomena invoked by sensory stimuli, which infers an internal representation of the structured events present in a piece of music and then forms long-term echoic memory for the music. An intrinsic relationship between the basic acoustic property (physics) of music and human emotional response (physiology) to the music is suggested, which can be statistically modeled and explained by using a novel notion termed as quantitative physics-physiology relationship (QPPR). Here, we systematically analyzed the complex response profile of people to traditional/ancient music in the Shu area, a geographical concept located in the Southwest China and one of three major origins of the Chinese nation. Chill was utilized as an indicator to characterize the response strength of 18 subjects to an in-house compiled repertoire of 86 music samples, consequently creating a systematic subject-to-sample response (SSTSR) profile consisting of 1,548 (18 × 86) paired chill elements. The multivariate statistical correlation of measured chill values with acoustic features and personal attributes was modeled by using random forest (RF) regression in a supervised manner, which was compared with linear partial least square (PLS) and non-linear support vector machine (SVM). The RF model exhibits possessed strong fitting ability (r F 2 = 0.857), good generalization capability (r P 2 = 0.712), and out-of-bag (OOB) predictability (r O 2 = 0.731) as compared to SVM and, particularly, PLS, suggesting that the RF-based QPPR approach is able to explain and predict the emotional change upon musical arousal. It is imparted that there is an underlying relationship between the acoustic physical property of music and the physiological reaction of the audience listening to the music, in which the rhythm contributes significantly to emotional response relative to timbre and pitch. In addition, individual differences, characterized by personal attributes, is also responsible for the response, in which gender and age are most important.

Tofacitinib for child-onset systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause diverse clinical manifestations in multiple organ systems. Child-onset SLE (cSLE) is associated with significantly higher morbidity and mortality than adult-onset SLE. The traditional treatments for SLE (glucocorticoids, antimalarials, conventional and biological disease-modifying antirheumatic drugs) often have significant adverse effects and may not fully control disease activity. Tofacitinib is an oral Janus kinase (JAK) inhibitor that inhibits the JAK-STAT pathway and has the potential to reduce SLE severity. Methods: cSLE patients who received tofacitinib and had at least one follow-up visit were retrospectively examined. Case histories, laboratory test results, and treatment regimens were analyzed at disease onset, initiation of tofacitinib treatment, and 1, 3, 6, 9, 12, 18, and 24 months after starting tofacitinib. Results: We examined 9 patients with refractory cSLE. All patients were female and the average age at diagnosis was 10.67 years. At initiation of tofacitinib, the average age was 13.28 years and the average disease duration was 2.62 years. Four patients experienced alleviation of symptoms and reduced their daily prednisone dosages; one of them also discontinued cyclosporine A and two of them also discontinued belimumab. The other 5 patients experienced no apparent benefit. Conclusion: Tofacitinib may provide clinical benefits for some patients with refractory cSLE, and can also allow reduction in the glucocorticoid dosage. Tofacitinib has the potential as an adjunctive treatment for some patients with cSLE.

Comprehensive Insight into the Common Organic Radicals in Advanced Oxidation Processes for Water Decontamination.

Radical-based advanced oxidation processes (AOPs) are among the most effective technologies employed to destroy organic pollutants. Compared to common inorganic radicals, such as •OH, O2•-, and SO4•-, organic radicals are widespread, and more selective, but are easily overlooked. Furthermore, a systematic understanding of the generation and contributions of organic radicals remains lacking. In this review, we systematically summarize the properties, possible generation pathways, detection methods, and contributions of organic radicals in AOPs. Notably, exploring organic radicals in AOPs is challenging due to (1) limited detection methods for generated organic radicals; (2) controversial organic radical-mediated reaction mechanisms; and (3) rapid transformation of organic radicals as reaction intermediates. In addition to their characteristics and reactivity, we examine potential scenarios of organic radical generation in AOPs, including during the peroxide activation process, in water matrices or with coexisting organic pollutants, and due to the addition of quenching agents. Subsequently, we summarize various methods for organic radical detection as reported previously, such as electron paramagnetic resonance spectroscopy (EPR), 31P nuclear magnetic resonance spectroscopy (31P NMR), liquid/gas chromatography-mass spectroscopy (GC/LC-MS), and fluorescence probes. Finally, we review the contributions of organic radicals to decontamination processes and provide recommendations for future research.

Ling-Gui-Zhu-Gan decoction inhibits cardiomyocyte pyroptosis via the NLRP3/Caspase-1 signaling pathway.

OBJECTIVE: The objective of this study was to investigate the protective mechanism of Ling-Gui-Zhu-Gan decoction (LGZGD) against LPS-ATP-induced pyroptosis in H9c2 cells. METHODS: LPS and ATP were used to induce pyroptosis in the H9c2 cell, and the cells were divided into the control, model and LGZGD groups. LDH level was detected using a colorimetric assay. ELISA was used to detect the expressions of IL-1ß. Flow cytometry was utilized to observe apoptosis, while Hoechst/PI staining was used to detect pyroptosis. Immunofluorescence was employed to observe the expression levels of NLRP3 in cardiomyocytes, and RT-PCR was used to detect NLRP3, Caspase-1, GSDMD, and ASC mRNA expression. The cells were separated into seven groups: control, model, LGZGD, MCC950, LGZGD+MCC950, Nigericin and LGZGD+Nigericin. The mRNA and protein expressions were determined by RT-PCR and Western blot. RESULTS: LPS (10 µg/mL) for 12 h and ATP (8 mM) for 2 h were used as modeling condition. LGZGD demonstrated a significant reduction in LDH, and IL-1ß levels (P<0.05, P<0.01). LGZGD dramatically reduced apoptosis rate, inhibited pyroptosis, decreased the fluorescence expressions of NLRP3, and reduced the mRNA expressions of NLRP3, ASC, Caspase-1, and GSDMD (P<0.01). Further mechanism studies showed that NLRP3, ASC, Caspase-1, and GSDMD decreased significantly when combined with NLRP3 inhibitor MCC950. Furthermore, LGZGD was able to effectively reverse the upregulation of protein and gene expression of Nigericin group (P<0.01). CONCLUSION: LGZGD inhibits LPS-ATP-induced pyroptosis in H9c2 cell via the NLRP3/Caspase-1 signaling pathway.

High drain field impact ionization transistors as ideal switches.

Impact ionization effect has been demonstrated in transistors to enable sub-60 mV dec-1 subthreshold swing. However, traditionally, impact ionization in silicon devices requires a high operation voltage due to limited electrical field near the device drain, contradicting the low energy operation purpose. Here, we report a vertical subthreshold swing device composed of a graphene/silicon heterojunction drain and a silicon channel. This structure creates a low voltage avalanche impact ionization phenomenon and leads to steep switching of the silicon-based device. Experimental measurements reveal a small average subthreshold swing of 16 µV dec-1 over 6 decades of drain current and nearly hysteresis-free, and the operating voltage at which a vertical subthreshold swing occurs can be as low as 0.4 V at room temperature. Furthermore, a complementary silicon-based logic inverter is experimentally demonstrated to reach a voltage gain of 311 at a supply voltage of 2 V.

Benzofurans and dibenzofurans from galls on twigs of the endangered Chinese endemic tree Parrotia subaequalis and their inhibitory properties against Staphylococcus aureus and ATP-citrate lyase.

Parrotia subaequalis, an endangered Tertiary relict tree native to China and a member of the Hamamelidaceae family, is one of several host plant species in this family that exhibit unique ecological habits, such as gall formation. Tree galls are the results of complex interactions between gall-inducing insects and their host plant organs. The formation of galls may serve to protect other regions of the plant from potential damage, often through the production of phytoalexins. In this study, a preliminary investigation was carried out on the metabolites of the 90% MeOH extract derived from the closed spherical galls on the twigs of P. subaequalis. Consequently, nine previously undescribed benzofuran-type and dibenzofuran-type phytoalexins (parrotiagallols A-I, 1-9, respectively) were isolated and characterized, along with several known miscellaneous metabolites (10-17). Their chemical structures and absolute configurations were elucidated using spectroscopic methods, a combination of calculated and experimental electronic circular dichroism data, and single crystal X-ray diffraction analyses. Among these compounds, 1 and 2 are identified as neolignan derivatives, while compounds 3-5 are classified as 9,10-dinorneolignans. Compound 6 represents a rare 2,3-seco-neolignan, and compounds 7-9 are dihydroxy-dimethyl-dibenzofuran derivatives. Parrotiagallol A (1) showed considerable antibacterial activity against Staphylococcus aureus, with an MIC value of 14 µM. Additionally, parrotiagallol E (5) and methyl gallate (17) exhibited inhibitory effects against ATP-citrate lyase (ACL), a potential therapeutic target for hyperlipidemia, with IC50 values of 5.1 and 9.8 µM, respectively. The findings underscore that galls not only serve as physical defense barriers but also benefit from the chemical defense system of the host plants. These insights provide avenues for exploring potential new therapeutic agents for S. aureus infections and ACL-related diseases, while also promoting scientific conservation strategies for P. subaequalis.

Multi-omics analysis uncovers the transcriptional regulatory mechanism of magnesium Ions in the synthesis of active ingredients in Sophora tonkinensis.

Magnesium (Mg) plays a pivotal role as an essential component of plant chlorophyll and functions as a critical coenzyme. However, research exploring the regulatory mechanisms of magnesium ions on the synthesis of secondary metabolites is still in its early stages. Sophora tonkinensis is a widely utilized medicinal plant in China, recognized for its diverse secondary metabolites with active properties. This study investigates variations in these ingredients in tissue-cultured seedlings under varying magnesium concentrations. Simultaneously, an omics data analysis was conducted on tissue-cultured seedlings subjected to treatments with magnesium and low magnesium. These comprehensive omics analyses aimed to elucidate the mechanisms through which magnesium influences active components, growth, and development. Magnesium exerts a pervasive influence on various metabolic pathways, forming an intricate network. Research findings indicate that magnesium impacts diverse metabolic processes, including the absorption of potassium and calcium, as well as photosynthetic activity. Consequently, these influences lead to discernible changes in the levels of pharmacologically active compounds and the growth and developmental status.This study is the first to employ a multi-omics data analysis in S. tonkinensis. This methodology allows us to uncover the overarching impact of metabolic networks on the levels of various active ingredients and specific phenotypes.

Retraction notice to "Protective effect of Huangpu Tongqiao capsule against Alzheimer's disease through inhibiting the apoptosis pathway mediated by endoplasmic reticulum stress in vitro and in vivo" [Saudi Pharm. J. 30(11) (2022) 1561-1571].

[This retracts the article DOI: 10.1016/j.jsps.2022.08.001.].

Difference in Allergenicity between ß-Lactoglobulin in Bovine Milk and Caprine Milk is Related to Their Respective Digestive Stability.

The underlying cause of differences in sensitization between bovine and caprine milk ß-lactoglobulin (ß-LG) remains unclear. In this study, denatured forms of bovine and caprine milk ß-LG were obtained through reductive alkylation and evaluated for allergenicity and digestibility in Balb/c mice. Results indicated weaker sensitization to nondenatured caprine milk ß-LG compared to nondenatured bovine milk ß-LG, with no significant difference in sensitization observed between denatured ß-LG from both sources. The nondenatured ß-LG of caprine milk and two types of denatured ß-LG were degraded more rapidly than nondenatured bovine milk ß-LG in the small intestine of mice. In terms of undenatured proteins, mouse intestinal tissues absorbed more bovine milk ß-LG than caprine milk ß-LG. Overall, structural disparities in ß-LG between bovine and caprine milk resulted in varying digestion rates. Moreover, the slower-degraded bovine milk ß-LG and its enzymatic fragments facilitated easier absorption by the intestine, disrupting the Th1/Th2 balance and increasing susceptibility to severe allergic reactions in mice.

Early-Life Milk αS1-Casein Allergy Induces the Activation of Astrocytes in Mice and Leads to Stress Vulnerability in Adulthood.

In recent years, the incidence of food allergies in children has been increasing annually, significantly affecting the quality of life for patients and their families. It has long been suspected that childhood allergies might potentially lead to behavioral and psychological issues in adulthood, but the specific connection remains unclear. In this study, we established a model of young mice allergic to milk αS1-casein, conducted behavioral tests, and employed transcriptomics, immunohistochemistry, Golgi staining, and fecal microbiota transplantation to explore the link between early life allergies and adult psychological problems. The results showed that early life milk protein allergy significantly increased intestinal epithelial permeability in mice, leading to the translocation of gut microbiota metabolites. This process subsequently activated astrocyte lysosomes via SLC15a3, making astrocytes more susceptible. This susceptibility caused mice with early life milk protein allergy to have more activated astrocytes and excessive dendritic spine phagocytosis (normal group: 5.4 ± 1.26 spines/10 µm, allergy group: 3.2 ± 0.92 spines/10 µm) under acute stress in adulthood, leading to anxiety and depressive behaviors.

Van der Waals integrated single-junction light-emitting diodes exceeding 10% quantum efficiency at room temperature.

The construction of miniaturized light-emitting diodes (LEDs) with high external quantum efficiency (EQE) at room temperature remains a challenge for on-chip optoelectronics. Here, we demonstrate microsized LEDs fabricated by a dry-transfer van der Waals (vdW) integration method using typical layered Ruddlesden-Popper perovskites (RPPs). A single-crystalline layered RPP nanoflake is used as the active layer and sandwiched between two few-layer graphene contacts, forming van der Waals LEDs (vdWLEDs). Strong electroluminescence (EL) emission with a low turn-on current density of ~20 pA µm-2 and high EQE exceeding 10% is observed at room temperature, which sets the benchmark for the EQE of vdWLEDs ever recorded. Such efficient EL emission is attributed to the inherent multiple quantum well structure and high photoluminescence quantum yield (~35%) of RPPs and a low charge injection barrier of ~0.10 eV facilitated by the Fowler-Nordheim tunneling mechanism. These findings promise a scalable pathway for accessing high-performance miniaturized light sources for on-chip optical optoelectronics.

Feasibility study of dual-accelerated simultaneous multi-slice imaging in diffusion tensor imaging of glioma.

Objective: To explore the value of dual-accelerated simultaneous multi-slice (SMS) imaging in diffusion tensor imaging (DTI) of glioma. Methods: Thirty-four patients with glioma who underwent magnetic resonance imaging (MRI) in our hospital from January 2022 to March 2023 were randomly selected. The results of dual-accelerated SMS-DTI and conventional DTI were retrospectively analyzed. All patients were scanned using a uMR790 3.0T MRI scanner, and the scanning technicians followed a predefined sequence to ensure consistency in scan parameters. The images were subjectively evaluated using a Likert 5-point scoring system. Objective evaluation was performed by measuring the required values of the images with b-value = 1000 s/mm2, primarily measuring the signal intensity in the tumor region and the contralateral normal brain white matter region. The standard deviation values were used to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the same encoding direction as the background noise. The number of generated fiber pathways, fractional anisotropy (FA), and mean diffusivity (MD) were measured and analyzed using post-processing software. The relative FA (rFA) and relative MD (rMD) were calculated. Results: The results of conventional DTI and SMS-accelerated DTI were compared. In terms of subjective evaluation, including overall image quality, tumor edge clarity, and magnetic sensitivity artifacts, both techniques showed no significant differences, indicating comparable diagnostic performance in anatomical visualization. In terms of objective evaluation and quantitative parameter measurement, there were statistically significant differences in SNR and CNR values, with slightly lower values in the dual-accelerated SMS-DTI compared with conventional DTI, a significant reduction in scanning time can be achieved through a slight loss in image quality. The number of fiber pathways and the rFA and rMD values did not show typical differences between the two techniques. The correlation between these measures was highly similar, with no significant differences observed. Conclusion: The application of dual-accelerated simultaneous multi-slice imaging in DTI of glioma is feasible.

Targeting the gut microbiota: a new strategy for colorectal cancer treatment.

BACKGROUND: How to reduce the high incidence rate and mortality of colorectal cancer (CRC) effectively is the focus of current research. Endoscopic treatment of early-stage CRC and colorectal adenomas (CAC) has a high success rate, but although several treatments are available for advanced CRC, such as surgery, radiotherapy, chemotherapy, and immunotherapy, the 5-year survival rate remains low. In view of the high incidence rate and mortality of CRC, early rational drug prevention for high-risk groups and exploration of alternative treatment modalities are particularly warranted. Gut microbiota is the target of and interacts with probiotics, prebiotics, aspirin, metformin, and various Chinese herbal medicines (CHMs) for the prevention of CRC. In addition, the anti-cancer mechanisms of probiotics differ widely among bacterial strains, and both bacterial strains and their derivatives and metabolites have been found to have anti-cancer effects. Gut microbiota plays a significant role in early drug prevention of CRC and treatment of CRC in its middle and late stages, targeting gut microbiota may be a new strategy for colorectal cancer treatment.

Mapping the research of nursing in Parkinson's disease: a bibliometric and quantitative analysis.

Background: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. Clinically, the therapeutic strategy of PD could only alleviate the symptoms. Nursing plays a crucial role in providing patient education, symptom management, and psychosocial support. This study aims to analyze the current state and prospects of research in the field of Parkinson's disease (PD) and its associated nursing care through bibliometric methods to explore the trends that May guide its future development. Methods: Literature related to Parkinson's disease and nursing care was systematically searched by the Web of Science database from 1991 to 2023. Quantitative analysis of cooperative networks was conducted using bibliometric tools VOSviewer and CiteSpace. Results: The analysis covered 2,649 publications in the field of PD and nursing care, authored by 12,576 researchers from 3,869 institutions across 94 countries. The number of articles has steadily increased over the past 20 years. In this research field, the United States and the United Kingdom emerged as leading countries, and Radboud Universiteit Nijmegen was positioned as an international hub. Movement Disorders was identified as the journal with the highest output and with the most co-citation. Prof. Bastiaan R. Bloem published the most papers in the area, and Prof. Per Odin had the highest average citation. The major fields of these publications are clinical neurology, geriatrics & gerontology, multidisciplinary sciences, and health care sciences & services. Hot topics in the field predominantly revolve around Parkinson's disease, quality of life, and dementia. Conclusion: Research in Parkinson's disease and nursing care is experiencing a period of rapid growth, with continuous expansion in research scope and depth of investigation. One of the trends identified is the increasing focus on quality of life and the management of dementia in PD patients, reflecting the importance of these areas in research. The study further suggests that future advancements in the field May rely significantly on strengthening international collaborations and addressing global disparities in resource distribution, particularly by promoting research inclusivity and cooperation among low-resource countries.

The neutrophil-lymphocyte ratio predicts all-cause and cardiovascular mortality among United States adults with COPD: results from NHANES 1999-2018.

Background: Neutrophil-to-lymphocyte ratio (NLR) is considered a biomarker of systemic inflammation and immune activation. However, its relationship with the risk of mortality in patients with chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the association between NLR and the risk of all-cause and cardiovascular mortality in patients with COPD. Methods: Data were collected from the National Health and Nutrition Examination Survey (NHANES) from January 1999 to December 2018. The calculation method of NLR involves dividing the neutrophil count by the lymphocyte count in the total blood cell count. The optimal NLR threshold associated with survival outcomes was determined using the maximally selected rank statistics method (MSRSM). The relationship between NLR and the risk of all-cause mortality and cardiovascular mortality in COPD was investigated using a weighted multivariable Cox regression model. Additionally, restricted cubic spline (RCS) was employed to discuss the potential relationship between NLR patients in different groups and the risk of mortality. Results: In this study, 716 adults with COPD were included using the maximally selected rank statistics method, among whom 208 had higher NLR (≥2.56) and 508 had lower NLR (<2.56). During a median follow-up of 111.5 months, 162 COPD patients died from all causes, and 49 patients died from cardiovascular diseases. After adjusting for demographic, socioeconomic status, and lifestyle factors, the risk of all-cause mortality (HR = 2.07, 95%CI: 1.46-2.94) and cardiovascular mortality (HR = 3.03, 95%CI: 1.63-5.65) in patients with higher NLR was increased by 2-3 times compared to those with lower NLR. Kaplan-Meier analysis revealed significantly lower survival rates in patients with higher NLR for all-cause mortality and cardiovascular mortality (p < 0.05). Restricted cubic spline analysis showed a linear correlation between NLR and the risk of all-cause mortality and cardiovascular mortality. Conclusion: NLR has a high value in independently predicting long-term all-cause and cardiovascular mortality risks in community-dwelling COPD patients. Therefore, NLR can serve as a cost-effective and widely available indicator for assessing the prognosis of COPD patients.

Gray matter and cognitive alteration related to chronic obstructive pulmonary disease patients: combining ALE meta-analysis and MACM analysis.

Chronic obstructive pulmonary disease (COPD) is frequently comorbid with cognitive impairment, but it has not been paid enough attention, and its neuroanatomical characteristics have not been fully identified. Voxel-based morphometric (VBM) studies comparing gray matter (GM) abnormalities in COPD patients with healthy controls (HCs) were searched using 8 electronic databases from the inception to March 2023. Stereotactic data were extracted and tested for convergence and differences using the activation likelihood estimation (ALE) method. Moreover, based on the ALE results, a structural meta-analytic connectivity modeling (MACM) was conducted to explore the co-atrophy pattern in patients with COPD. Last, behavioral analysis was performed to assess the functional roles of the regions affected by COPD. In total, 11 studies on COPD with 949 participants were included. Voxel-based meta-analysis revealed significant GM abnormalities in the right postcentral gyrus (including inferior parietal lobule), left precentral gyrus, and left cingulate gyrus (including paracentral lobule) in patients with COPD compared with HCs. Further MACM analysis revealed a deeper co-atrophy pattern between the brain regions with abnormal GM structure and the insula in COPD patients. Behavioral analysis showed that the abnormal GM structure in the left cingulate gyrus (including paracentral lobule) was strongly associated with cognitive function, especially executive function. COPD comorbid with cognitive impairment has a specific neurostructural basis of GM structural abnormalities, which may also involve a deeper co-atrophy pattern between the insula. These findings enhance our understanding of the underlying neuropathogenesis and suggest potential imaging markers for cognitive impairment in COPD patients. PROSPERO registration number: CRD42022298722.

RAG-seq: A NSR Primed and Transposase Tagmentation Mediated Strand-specific Total RNA Sequencing in Single Cell.

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of cellular diversity with unprecedented resolution. However, many current methods are limited in capturing full-length transcripts and discerning strand orientation. We present RAG-seq, an innovative strand-specific total RNA sequencing technique that combines not-so-random (NSR) primers with Tn5 transposase-mediated tagmentation. RAG-seq overcomes previous limitations by delivering comprehensive transcript coverage and maintaining strand orientation, which is essential for accurate quantification of overlapping genes and detection of antisense transcripts. Through optimized reverse transcription with oligo dT primers, rRNA depletion via Depletion of Abundant Sequences by Hybridization (DASH), and linear amplification, RAG-seq enhances sensitivity and reproducibility, especially for low-input samples and single cells. Application to mouse oocytes and early embryos highlights RAG-seq's superior performance in identifying stage-specific antisense transcripts, shedding light on their regulatory roles during early development. This advancement represents a significant leap in transcriptome analysis within complex biological contexts.

Combination of intravoxel incoherent motion histogram parameters and clinical characteristics for predicting response to neoadjuvant chemoradiation in patients with locally advanced rectal cancer.

OBJECTIVE: To explore the value of histogram parameters derived from intravoxel incoherent motion (IVIM) for predicting response to neoadjuvant chemoradiation (nCRT) in patients with locally advanced rectal cancer (LARC). METHODS: A total of 112 patients diagnosed with LARC who underwent IVIM-DWI prior to nCRT were enrolled in this study. The true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and microvascular volume fraction (f) calculated from IVIM were recorded along with the histogram parameters. The patients were classified into the pathological complete response (pCR) group and the non-pCR group according to the tumor regression grade (TRG) system. Additionally, the patients were divided into low T stage (yp T0-2) and high T stage (ypT3-4) according to the pathologic T stage (ypT stage). Univariate logistic regression analysis was implemented to identify independent risk factors, including both clinical characteristics and IVIM histogram parameters. Subsequently, models for Clinical, Histogram, and Combined Clinical and Histogram were constructed using multivariable binary logistic regression analysis for the purpose of predicting pCR. The area under the receiver operating characteristic (ROC) curve (AUCs) was employed to evaluate the diagnostic performance of the three models. RESULTS: The values of D_ kurtosis, f_mean, and f_ median were significantly higher in the pCR group compared with the non-pCR group (all P < 0.05). The value of D*_ entropy was significantly lower in the pCR group compared with the non-pCR group (P < 0.05). The values of D_ kurtosis, f_mean, and f_ median were significantly higher in the low T stage group compared with the high T stage group (all P < 0.05). The value of D*_ entropy was significantly lower in the low T stage group compared with the high T stage group (P < 0.05). The ROC curves indicated that the Combined Clinical and Histogram model exhibited the best diagnostic performance in predicting the pCR patients with AUCs, sensitivity, specificity, and accuracy of 0.916, 83.33%, 85.23%, and 84.82%. CONCLUSIONS: The histogram parameters derived from IVIM have the potential to identify patients who have achieved pCR. Moreover, the combination of IVIM histogram parameters and clinical characteristics enhanced the diagnostic performance of IVIM histogram parameters.