Creating a bacterium that forms eukaryotic nucleosome core particles.

The nucleosome is one of the hallmarks of eukaryotes, a dynamic platform that supports many critical functions in eukaryotic cells. Here, we engineer the in vivo assembly of the nucleosome core in the model bacterium Escherichia coli. We show that bacterial chromosome DNA and eukaryotic histones can assemble in vivo to form nucleosome complexes with many features resembling those found in eukaryotes. The formation of nucleosomes in E. coli was visualized with atomic force microscopy and using tripartite split green fluorescent protein. Under a condition that moderate histones expression was induced at 1 µM IPTG, the nucleosome-forming bacterium is viable and has sustained growth for at least 110 divisions in longer-term growth experiments. It exhibits stable nucleosome formation, a consistent transcriptome across passages, and reduced growth fitness under stress conditions. In particular, the nucleosome arrays in E. coli genic regions have profiles resembling those in eukaryotic cells. The observed compatibility between the eukaryotic nucleosome and the bacterial chromosome machinery may reflect a prerequisite for bacteria-archaea union, providing insight into eukaryogenesis and the origin of the nucleosome.

Pseudo-CT synthesis in adaptive radiotherapy based on a stacked coarse-to-fine model: Combing diffusion process and spatial-frequency convolutions.

BACKGROUND: Cone beam computed tomography (CBCT) provides critical anatomical information for adaptive radiotherapy (ART), especially for tumors in the pelvic region that undergo significant deformation. However, CBCT suffers from inaccurate Hounsfield Unit (HU) values and lower soft tissue contrast. These issues affect the accuracy of pelvic treatment plans and implementation of the treatment, hence requiring correction. PURPOSE: A novel stacked coarse-to-fine model combining Denoising Diffusion Probabilistic Model (DDPM) and spatial-frequency domain convolution modules is proposed to enhance the imaging quality of CBCT images. METHODS: The enhancement of low-quality CBCT images is divided into two stages. In the coarse stage, the improved DDPM with U-ConvNeXt architecture is used to complete the denoising task of CBCT images. In the fine stage, the deep convolutional network model jointly constructed by fast Fourier and dilated convolution modules is used to further enhance the image quality in local details and global imaging. Finally, the accurate pseudo-CT (pCT) images consistent with the size of the original data are obtained. Two hundred fifty paired CBCT-CT images from cervical and rectal cancer, combined with 200 public dataset cases, were used collectively for training, validation, and testing. RESULTS: To evaluate the anatomical consistency between pCT and real CT, we have used the mean(std) of structure similarity index measure (SSIM), peak signal to noise ratio (PSNR), and normalized cross-correlation (NCC). The numerical results for the above three metrics comparing the pCT synthesized by the proposed model against real CT for cervical cancer cases were 87.14% (2.91%), 34.02 dB (1.35 dB), and 88.01% (1.82%), respectively. For rectal cancer cases, the corresponding results were 86.06% (2.70%), 33.50 dB (1.41 dB), and 87.44% (1.95%). The paired t-test analysis between the proposed model and the comparative models (ResUnet, CycleGAN, DDPM, and DDIM) for these metrics revealed statistically significant differences (p < 0.05). The visual results also showed that the anatomical structures between the real CT and the pCT synthesized by the proposed model were closer. For the dosimetric verification, mean absolute error of dosimetry (MAEdoes) values for the maximum dose (Dmax), the minimum dose (Dmin), and the mean dose (Dmean) in the planning target volume (PTV) were analyzed, with results presented as mean (lower quartile, upper quartile). The experimental results show that the values of the above three dosimetry indexes (Dmin, Dmax, and Dmean) for the pCT images synthesized by the proposed model were 0.90% (0.48%, 1.29%), 0.82% (0.47%, 1.17%), and 0.57% (0.44%, 0.67%). Compared with 10 cases of the original CBCT image by Mann-Whitney test (p < 0.05), it also proved that pCT can significantly improve the accuracy of HU values for the dose calculation. CONCLUSION: The pCT synthesized by the proposed model outperforms the comparative models in numerical accuracy and visualization, promising for ART of pelvic cancers.

Curcumin and nanodelivery systems: New directions for targeted therapy and diagnosis of breast cancer.

As the global incidence of breast cancer continues to surge, the pursuit of novel, low-toxicity, and highly efficacious therapeutic strategies has emerged as a pivotal research focus. Curcumin (CUR), an active constituent of traditional Chinese medicine (TCM) renowned for its antimicrobial, anti-inflammatory, antioxidant, and antitumor properties, exhibits immense potential in breast cancer therapy. Nevertheless, CUR's poor water solubility, chemical instability, and unfavorable pharmacokinetics have impeded its clinical utilization. To address these challenges, nano-delivery systems have been extensively exploited for CUR administration, enhancing its in vivo stability and bioavailability, and facilitating precise targeting of breast cancer lesions. Therefore, we elaborate on CUR's chemical foundations, drug metabolism, and safety profile, and elucidate its potential mechanisms in breast cancer therapy, encompassing inducing apoptosis and autophagy, blocking cell cycle, inhibiting breast cancer metastasis, regulating tumor microenvironment and reversing chemotherapy resistance. The review primarily emphasizes recent advancements in CUR-based nano-delivery systems for the treatment and diagnosis of breast cancer. Liposomes, nanoparticles (encompassing polymer nanoparticles, solid lipid nanoparticles, mesoporous silica particles, metal/metal oxide nanoparticles, graphene nanomaterials, albumin nanoparticles, etc.), nanogels, and nanomicelles can serve as delivery carriers for CUR, exhibiting promising anti-breast cancer effects in both in vivo and in vitro experiments. Furthermore, nano-CUR can be integrated with fluorescence imaging, magnetic resonance imaging, computed tomography imaging, ultrasound, and other techniques to achieve precise localization and diagnosis of breast cancer masses. While this article has summarized the clinical studies of nano-curcumin, it is noteworthy that the research literature on nano-CUR applied to breast cancer diagnosis and the translation of nano-CUR clinical studies in BC patients remain limited. Therefore, future research should intensify exploration in this direction.

A2HTL: An Automated Hybrid Transformer Based Learning for Predicting Survival of Esophageal Cancer Using CT Images.

Esophageal cancer is a common malignant tumor, precisely predicting survival of esophageal cancer is crucial for personalized treatment. However, current region of interest (ROI) based methodologies not only necessitate prior medical knowledge for tumor delineation, but may also cause the model to be overly sensitive to ROI. To address these challenges, we develop an automated Hybrid Transformer based learning that integrates a Hybrid Transformer size-aware U-Net with a ranked survival prediction network to enable automatic survival prediction for esophageal cancer. Specifically, we first incorporate the Transformer with shifted windowing multi-head self-attention mechanism (SW-MSA) into the base of the UNet encoder to capture the long-range dependency in CT images. Furthermore, to alleviate the imbalance between the ROI and the background in CT images, we devise a size-aware coefficient for the segmentation loss. Finally, we also design a ranked pair sorting loss to more comprehensively capture the ranked information inherent in CT images. We evaluate our proposed method on a dataset comprising 759 samples with esophageal cancer. Experimental results demonstrate the superior performance of our proposed method in survival prediction, even without ROI ground truth.

Novel insights: crosstalk with non-puerperal mastitis and immunity.

The two primary types of non-puerperal mastitis (NPM) are granulomatous lobular mastitis (GLM) and plasma cell mastitis (PCM). Existing research indicates that immune inflammatory response is considered to be the core of the pathogenesis of GLM and PCM, and both innate and adaptive immune responses play an important role in the pathophysiology of PCM and GLM. However, the regulatory balance between various immune cells in these diseases is still unclear. Consequently, we present a comprehensive summary of the immune-related variables and recent advances in GLM and PCM.

A 3-year follow-up analysis of renal function in elderly patients with type 2 diabetes mellitus and an estimated glomerular filtration rate <90 mL/min/1.73m2: A retrospective cohort study.

Type 2 diabetes mellitus (T2DM) is a risk factor for patients with impaired renal function. The onset of T2DM-induced diabetic kidney disease (DKD) is frequently sub-clinical, potentially culminating in end-stage renal disease. In the current study the factors influencing DKD in elderly patients diagnosed with T2DM were determined. A retrospective cohort study was conducted involving patients ≥60 years of age with T2DM from June 2019 to December 2022. The Cockcroft-Gault formula was used to estimate the glomerular filtration rate. The clinical information and biochemical indicators of patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were collected. Patients were grouped based on a 3-year eGFR decline < 15% and ≥ 15%. The differences between the two groups were compared and the factors influencing the 3-year eGFR decline ≥ 15% were analyzed. A total of 242 patients were included, including 154 in the group with a 3-year eGFR decline < 15% and 88 in the group with a three-year eGFR decline ≥ 15%. Univariate logistic regression analysis showed that smoking cigarettes, and triglycerides (TG) and high-density lipoprotein levels were related to a 3-year eGFR decline ≥ 15% (P = .039, P < .001, and P = .011, respectively). Multivariate logistic regression analysis showed that the TG level was independently related to a 3-year eGFR decline ≥ 15% (P = .004; OR = 2.316). There was a significant linear relationship between the eGFR decline and TG level (P = .002). Patients with a TG concentration > 1.7 mmol/L had a more apparent decrease in the eGFR (P < .05). For elderly patients with T2DM and an eGFR < 90 mL/min/1.73m2, the TG level may be an important risk factor for deteriorating renal function that warrants actively intervention.

Zebrafish myo7aa affects congenital hearing by regulating Rho-GTPase signaling.

Introduction: myo7aa, the homolog of the human Usher 1B syndrome pathogenic gene, myo7A, plays an important role in stereociliary development and maintenance, therefore, is critical for hearing and balance. However, the molecular mechanisms that myo7aa regulate hearing and balance still need to be studied. Methods: In this study, we generated two independent zebrafish myo7aa knockout lines using CRISPR/Cas9 technology. To investigate the effects of myo7aa on hearing, YO-PRO-1 staining and startle response assay were used. To gain insight into the specific molecular mechanisms by which myo7aa affects hearing, transcriptome sequencing and bioinformatics analysis were employed. Results: Our study showed that hair cells of myo7aa-/- zebrafish can not take up YO-PRO-1 fluorescent dye and are insensitive to acoustic stimulation in myo7aa-/- zebrafish compared to wild type. Genes related to the Rho GTPase signaling pathway, such as arhgap33, dab2ip, and arghef40, are significantly down-regulated in myo7aa-/- zebrafish embryos at 3 dpf. GTP and ATP compensation can partially rescue the hair cell defects in myo7aa knockout zebrafish. Discussion: Our findings suggest that zebrafish myo7aa affects congenital hearing by regulating Rho GTPase signaling, and loss of myo7aa leads to abnormal Rho GTPase signaling and impairs hair cell function. myo7aa, myo7A, arhgap33, dab2ip, arghef40 and myo7aa-/- fonts in the abstract are italicized. -/- is a superscript format.

Pre-Coordination Induced Further Deamination to Create Inter-Chain Cross-Linking in Carbon Nitride for Enhanced Photocatalytic H2O2 Production.

Creating cross-linking to establish efficient inter-chain charge-transfer channels in carbon nitride represents a promising strategy for enhancing its photocatalytic capabilities. Molten salt-assisted calcining has emerged as a method for preparing cross-linked carbon nitrides. However, the precise influence of molten salts on the molecular structure of carbon nitride remains to be fully elucidated. Herein, we develop a KCl guided cross-linking reaction to preliminarily reveal the formation mechanism of cross-linking. The cross-linking reaction is initiated by the pre-coordination of amino groups with K+. Subsequent heating at high temperature converts the amino groups into chlorines. Then, dechlorination leads to the formation of cross-linking. Thus, this cross-linking reaction can be accurately described as a pre-coordination-induced, two-step deamination reaction. The pre-coordination step plays a pivotal role in the cross-linking process. Sufficient pre-coordination results in a relatively high cross-linking degree of the as-prepared CNK-2. Consequently, CNK-2 demonstrates a significantly enhanced photocatalytic H2O2 production, with a generation rate of 682 µmol L-1 h-1, about 59 times that of traditional carbon nitride.

Phase I clinical trial of intracerebral injection of lentiviral-ABCD1 for the treatment of cerebral adrenoleukodystrophy.

This was a single-arm, multicenter, open-label phase I trial. Lentiviral vectors (LV) carrying the ABCD1 gene (LV-ABCD1) was directly injected into the brain of patients with childhood cerebral adrenoleukodystrophy (CCALD), and multi-site injection was performed. The injection dose increased from 200 to 1600 µL (vector titer: 1×109 transduction units per mL (TU/mL)), and the average dose per kilogram body weight ranges from 8 to 63.6 µL/kg. The primary endpoint was safety, dose-exploration and immunogenicity and the secondary endpoint was initial evaluation of efficacy and the expression of ABCD1 protein. A total of 7 patients participated in this phase I study and were followed for 1 year. No injection-related serious adverse event or death occurred. Common adverse events associated with the injection were irritability (71%, 5/7) and fever (37.2-38.5 â„ƒ, 57%, 4/7). Adverse events were mild and self-limited, or resolved within 3 d of symptomatic treatment. The maximal tolerable dose is 1600 µL. In 5 cases (83.3%, 5/6), no lentivirus associated antibodies were detected. The overall survival at 1-year was 100%. The ABCD1 protein expression was detected in neutrophils, monocytes and lymphocytes. This study suggests that the intracerebral injection of LV-ABCD1 for CCALD is safe and can achieve successful LV transduction in vivo; even the maximal dose did not increase the risk of adverse events. Furthermore, the direct LV-ABCD1 injection displayed low immunogenicity. In addition, the effectiveness of intracerebral LV-ABCD1 injection has been preliminarily demonstrated while further investigation is needed. This study has been registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/, registration number: ChiCTR1900026649).

The application of DPE, CSEA, and EA in labor analgesia for nulliparous women and their impact on maternal and infant safety.

This work compared the effects of dural puncture epidural (DPE), combined spinal epidural analgesia (CSEA) and epidural analgesia (EA) on labor analgesia for primiparae and their impacts on maternal and infant safety. A total of 204 primiparae in need of labor analgesia for vaginal delivery were allocated to DPE, CSEA and EA groups. At 10 min, 30 min and 1 h after analgesia, the DPE and CSEA groups showed lower VAS scores and quicker onset of action than EA group. There was no significant difference in the duration of analgesia and labor and fetal decelerations among the 3 groups. At 1 min and 5 min after childbirth, the neonatal Apgar scores showed no significant difference between the 3 groups. The Bromage scores of DPE and EA groups were lower than those of CSEA group. The incidence of pruritus, hypotension, and postpartum headache in DPE and EA groups were lower than those in CSEA group. To sum up, the efficacy of DPE in labor analgesia for primiparae is similar to that of CSEA, with no obvious effect on labor stage and neonatal Apgar score, no additional complications and less LLMB, pruritus, hypotension and postpartum headache.

Chinese Emotional Speech Audiometry Project (CESAP): Establishment and Validation of a New Material Set With Emotionally Neutral Disyllabic Words.

PURPOSE: The Chinese Emotional Speech Audiometry Project (CESAP) aims to establish a new material set for Chinese speech audiometry tests, which can be used in both neutral and emotional prosody settings. As the first endeavor of CESAP, this study demonstrates the development of the material foundation and reports its validation in neutral prosody. METHOD: In the development step, 40 phonetically balanced word lists consisting of 30 Chinese disyllabic words with neutral valence were first generated. In a following affective rating experiment, 35 word lists were qualified for validation based on the familiarity and valence ratings from 30 normal-hearing (NH) participants. For validation, performance-intensity functions of each word list were fitted with responses from 60 NH subjects under six presentation levels (-1, 3, 5, 7, 11, and 20 dB HL). The final material set was determined by the intelligibility scores at each decibel level and the mean slopes. RESULTS: First, 35 lists satisfied the criteria of phonetic balance, limited repetitions, high familiarity, and neutral valence and were selected for validation. Second, 15 lists were compiled in the final material set based on the pairwise differences in intelligibility scores and the fitted 20%-80% slopes. The established material set had high reliability and validity and was sensitive to detect intelligibility changes (50% slope: 6.20%/dB; 20%-80% slope: 5.45%/dB), with small covariance of variation for thresholds (15%), 50% slope (12%), and 20%-80% slope (12%). CONCLUSION: Our final material set of 15 word lists takes the initiative to control the emotional aspect of audiometry tests, which enriches available Mandarin speech recognition materials and warrants future assessments in emotional prosody among populations with hearing impairments. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25742814.

Preparation of Zn/Zr-MOFs by microwave-assisted ball milling and adsorption of lomefloxacin hydrochloride and levofloxacin hydrochloride in wastewater.

The Zn/Zr-MOFs were synthesized via microwave-assisted ball milling and subsequently characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The thermal stability of the Zn/Zr-MOFs was evaluated through thermogravimetry (TGA). The results demonstrated the exceptional adsorption properties of the Zn/Zr-MOFs towards Lomefloxacin hydrochloride and Levofloxacin hydrochloride. At a concentration of 30 ppm for Lomefloxacin hydrochloride, the addition of 30 mg of Zn/Zr-MOFs material resulted in an adsorption capacity of 179.2 mg•g-1. Similarly, at a concentration of 40 ppm for Levofloxacin hydrochloride, the addition of 30 mg Zn/Zr-MOFs material led to an adsorption capacity of 187.1 mg•g-1. Kinetic analysis revealed that the experimental data aligned well with a pseudo-second order kinetic model. Overall, these findings highlight the significant potential application of Zn/Zr-MOF materials in wastewater treatment.

The comorbid network characteristics of anxiety and depressive symptoms among Chinese college freshmen.

BACKGROUND: This study aimed to investigate the interplay between anxiety and depressive symptoms in Chinese college freshmen using the causal system perspective (CSP), which differs from the traditional common cause perspective (CCP) by providing an alternative explanation by attributing comorbidity to direct interactions among symptoms. METHODS: A convenience sample of 2,082 Chinese college freshmen (39.51% male, Mage = 18.61) from a normal university completed the Generalized Anxiety Disorder 7-Item Scale (GAD-7) and the Patient Health Questionnaire (PHQ-9). Network analysis was conducted and evaluated as to centrality, stability, node predictability, and bridging features. Moreover, the moderated network model (MNM) was utilized to detect the moderation effects of gender in the comorbidity network. RESULTS: The network of anxiety and depressive symptoms exhibited stability, characterized by the core symptoms of "restlessness", "lack of energy", and "excessive worry about control", as well as the bridging symptoms of "fearfulness", "sad mood", and "irritability". Notably, the nodes representing "uncontrollable worry" and "difficulty in relaxation" demonstrated the highest predictive power. Gender did not exert any moderating effects on the anxiety and depressive symptom network. CONCLUSION: These results reinforce that certain anxiety or depressive symptoms are more central than others, and thus play a more vital role in the comorbid network. These findings highlight underlying potential targeting symptoms to consider in future interventions.

Aquaporins enriched in endothelial vacuole membrane regulate the diameters of microvasculature in hyperglycaemia.

AIMS: In patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. Yet, the regulatory mechanism and effective treatment approach remain elusive. METHODS AND RESULTS: Our initial findings revealed a notable decrease in the expression of human AQP1 in both diabetic human retina samples (49 healthy vs. 54 diabetic samples) and high-glucose-treated human retinal microvascular endothelial cells. Subsequently, our investigations unveiled a reduction in vascular diameter and compromised perfusion within zebrafish embryos subjected to high glucose treatment. Further analysis indicated a significant down-regulation of two aquaporins, aqp1a.1 and aqp8a.1, which are highly enriched in ECs and are notably responsive to hyperglycaemic conditions. Intriguingly, the loss of function of aqp1a.1 and/or aqp8a.1 resulted in a reduction of intersegmental vessel diameters, effectively mirroring the phenotype observed in the hyperglycaemic zebrafish model. The overexpression of aqp1a.1/aqp8a.1 in zebrafish ECs led to notable enlargement of microvascular diameters. Moreover, the reduced vessel diameters resulting from high-glucose treatment were effectively rescued by the overexpression of these aquaporins. Additionally, both aqp1a.1 and apq8a.1 were localized in the intracellular vacuoles in cultured ECs as well as the ECs of sprouting ISVs, and the loss of Aqps caused the reduction of those vacuoles, which was required for lumenization. Notably, while the loss of AQP1 did not impact EC differentiation from human stem cells, it significantly inhibited vascular formation in differentiated ECs. CONCLUSION: EC-enriched aquaporins regulate the diameter of blood vessels through an intracellular vacuole-mediated process under hyperglycaemic conditions. These findings collectively suggest that aquaporins expressed in ECs hold significant promise as potential targets for gene therapy aimed at addressing vascular perfusion defects associated with diabetes.

Proteomic Identification of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratification.

Diagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared to low-risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification.

Classification of nomophobia among Chinese college students: Evidence from latent profile and ROC analysis.

Background and aims: Nomophobia (NMP) is a contemporary digital ailment referring to the improper utilization of smartphones which can have significant impacts on the physical and mental health of college students. However, as a result of unclear cutoff points, the proportion of people with NMP may be exaggerated. This study therefore aimed to determine the critical value of NMP and assess the extent to which Chinese college students are impacted by NMP using the Nomophobia Questionnaire (NMP-Q). Methods: Latent profile analysis (LPA) and the receiver operating characteristic curve (ROC) were combined to determine the critical value based on NMP-Q scores using a large sample of 3,998 college students (Mage = 20.58; SD = 1.87). Results: Based on latent profile (i.e., at-risk NMP group), ROC revealed an optimal cut-off point of 73 (Sensitivity = 0.965, Specificity = 0.970, Accuracy = 0.968, AUC = 99.60%, Youden's index = 0.935), and the percentage of NMP students being 28.04%, with 1,121 participants identified as positive cases (probable cases). Positive cases were found to exhibit more severe depression and anxiety symptoms, with a higher proportion of females were observed in the positive group (N = 829; 73.95%). Conclusions: These findings provide evidence that the proportion of NMP individuals may have been overestimated in the past. Furthermore, this study helps to validate the NMP-Q as a valid tool to identify NMP in college-aged individuals.

[Research progress on structures, activities, and biosynthesis of blazeispirol compounds from Agaricus blazei].

Agaricus blazei is a rare medicinal and edible fungus with a crispy taste and delicious flavor. Both fruiting body and mycelium are rich in polysaccharides, sterols, terpenoids, peptides, lipids, polyphenols, and other active ingredients, which have strong pharmacological activities such as anti-tumor, lipid-lowering, glucose-lowering, immunomodulation, optimization of intestinal flora, and anti-oxidation. Therefore, it is a kind of fungal resource with a great prospect of edible and medicinal development. Among the reported chemical components of A. blazei, blazeispirol is a series of sterol compounds unique to A. blazei, which has a spiral structure and is different from classical steroids. It is an important active ingredient found in the mycelium of A. blazei and has significant hepatoprotective activity. It can be used as a phylogenetic and chemotaxonomic marker of A. blazei strains and is considered an excellent lead compound for drug development. According to the skeleton structure characteristics, the 17 discovered blazeispirol compounds can be divided into two types: blazeispirane and problazeispirane. In order to further explore the resource of blazeispirol compounds of A. blazei, the discovery, isolation, structure, biological activity, and biosynthetic pathways of blazeispirol compounds of A. blazei were systematically reviewed. Besides, the metabolic regulation strategies related to the fermentation synthesis of blazeispirol A by A. blazei were discussed. This review could provide a reference for the efficient synthesis and development of blazeispirol compounds, the research and development of related drugs and functional foods, and the quality improvement of A. blazei and other medicinal and edible fungi resources and derivatives.

Clinical-radiomics nomogram for the risk prediction of esophageal fistula in patients with esophageal squamous cell carcinoma treated with intensity-modulated radiation therapy or volumetric-modulated arc therapy.

Background: Esophageal fistula (EF) is a serious adverse event as a result of radiotherapy in patients with esophageal cancer (EC). We aimed to identify the predictive factors and establish a prediction model of EF in patients with esophageal squamous cell carcinoma (ESCC) who underwent intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Methods: Patients with ESCC treated with IMRT or VMAT from January 2013 to December 2020 at Xijing Hospital were retrospectively analyzed. Ultimately, 43 patients with EF and 129 patients without EF were included in the analysis and propensity-score matched in a 1:3 ratio. The clinical characteristics and radiomics features were extracted. Univariate and multivariate stepwise logistic regression analyses were used to determine the risk factors associated with EF. Results: The median follow-up time was 24.0 months (range, 1.3-104.9 months), and the median overall survival (OS) was 13.1 months in patients with EF. A total of 1,158 radiomics features were extracted, and eight radiomics features were selected for inclusion into a model for predicting EF, with an area under the receiver operating characteristic curve (AUC) value of 0.794. Multivariate analysis showed that tumor length, tumor volume, T stage, lymphocyte rate (LR), and grade IV esophagus stenosis were related to EF, and the AUC value of clinical model for predicting EF was 0.849. The clinical-radiomics model had the best performance in predicting EF with an AUC value of 0.896. Conclusions: The clinical-radiomics nomogram can predict the risk of EF in ESCC patients and is helpful for the individualized treatment of EC.

A novel GARP humanized mouse model for efficacy assessment of GARP-targeting therapies.

Although breakthroughs have been achieved with immune checkpoint inhibitors (ICI) therapy, some tumors do not respond to those therapies due to primary or acquired resistance. GARP, a type I transmembrane cell surface docking receptor mediating latent transforming growth factor-ß (TGF-ß) and abundantly expressed on regulatory T lymphocytes and platelets, is a potential target to render these tumors responsive to ICI therapy, and enhancing anti-tumor response especially combined with ICI. To facilitate these research efforts, we developed humanized mouse models expressing humanized GARP (hGARP) instead of their mouse counterparts, enabling in vivo assessment of GARP-targeting agents. We created GARP-humanized mice by replacing the mouse Garp gene with its human homolog. Then, comprehensive experiments, including expression analysis, immunophenotyping, functional assessments, and pharmacologic assays, were performed to characterize the mouse model accurately. The Tregs and platelets in the B-hGARP mice (The letter B is the first letter of the company's English name, Biocytogen.) expressed human GARP, without expression of mouse GARP. Similar T, B, NK, DCs, monocytes and macrophages frequencies were identified in the spleen and blood of B-hGARP and WT mice, indicating that the humanization of GARP did not change the distribution of immune cell in these compartments. When combined with anti-PD-1, monoclonal antibodies (mAbs) against GARP/TGF-ß1 complexes demonstrated enhanced in vivo anti-tumor activity compared to monotherapy with either agent. The novel hGARP model serves as a valuable tool for evaluating human GARP-targeting antibodies in immuno-oncology, which may enable preclinical studies to assess and validate new therapeutics targeting GARP. Furthermore, intercrosses of this model with ICI humanized models could facilitate the evaluation of combination therapies.

Dataset on the effects of psychological care on depression and suicide ideation in underrepresented children.

Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and "left-behind" and "single-parenting" children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.